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BIOMARKER:

CD73 expression

i
Other names: CD73, 5'-Nucleotidase Ecto, Ecto-5'-Nucleotidase, 5'-Nucleotidase, 5'-NT, NT5, NTE, 5'-Nucleotidase, Ecto (CD73), Purine 5-Prime-Nucleotidase, 5' Nucleotidase (CD73), CD73 Antigen, E5NT
2d
Combination of oxaliplatin and POM-1 by nanoliposomes to reprogram the tumor immune microenvironment. (PubMed, J Control Release)
The designed POL can effectively inhibit the growth of in situ, lung metastasis and postoperative recurrence melanoma model and form long-term immune memory. With the powerful clinical transformation potential of nanoliposome platforms, this new synergistic strategy is expected to enhance anticancer effects safely and effectively.
Journal
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ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
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CD73 expression
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oxaliplatin
2d
The regulation of CD73 in non-small cell lung cancer. (PubMed, Eur J Cancer)
Higher CD73 expression in NSCLC cancer cells and patient-derived organoids with EGFR mutation, KRAS mutation or ALK-rearrangement. Mechanistically, CD73 is regulated by ERK-Jun pathway, wherein c-Jun regulates CD73 expression via binding to CD73 genomic regions.
Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • NT5E (5'-Nucleotidase Ecto) • JUN (Jun proto-oncogene)
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PD-L1 expression • KRAS mutation • EGFR mutation • ALK positive • ALK rearrangement • TMB-L • CD73 overexpression • CD73 expression • NT5E overexpression
4d
RAS and BRAF mutations in colorectal cancer drive CD73 expression associated with oxaliplatin resistance and an immunosuppressed phenotype. (EACR 2022)
CD73 protein levels were analyzed by IHC in TMAs from 119 patient tumor samples treated with first-line oxaliplatin- (N=76) or irinotecan-based schedules (N=35). Conclusion Our in vitro, clinical and in silico data suggests a link between CD73; RAS/BRAF mutations, resistance to oxaliplatin and an immunosuppressed profile. CRC patients with RAS/BRAF mutant-tumors may benefit from combinations of CD73 inhibitor and oxaliplatin with or without immunotherapy.
IO biomarker
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BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • CD4 (CD4 Molecule) • SLC29A1 (Solute Carrier Family 29 Member 1) • NT5E (5'-Nucleotidase Ecto)
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KRAS mutation • BRAF mutation • KRAS G12V • BRAF wild-type • KRAS wild-type • RAS wild-type • RAS mutation • KRAS G12 • CD73 expression
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oxaliplatin • irinotecan
4d
Uncovering a new regulatory γδ T cell subpopulation in human solid cancers (EACR 2022)
Our data show different immediate ecosystems for CD73+ compared to CD73- γδ TILs, with more blood vessels and cancer-associated fibroblasts in contact with CD73+ γδ TILs, while CD73- γδ TILs interact more with activated αβ TILs reinforcing the idea that CD73+ and CD73- γδ T cells are functionally different. Conclusion Altogether, these data improve our knowledge on human γδ T cell immunobiology during cancer development, with the in-depth characterization of the new regulatory γδ T cell subset, their localization and their functions within the TME.
Clinical
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CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL10 (Interleukin 10) • NT5E (5'-Nucleotidase Ecto)
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CD73 expression
8d
CD73 downregulation by EGFR-targeted liposomal CD73 siRNA potentiates antitumor effect of liposomal doxorubicin in 4T1 tumor-bearing mice. (PubMed, Sci Rep)
GE11-Lipo CD73 siRNA formulation can efficiently knockdown CD73 ectonucleotidase. Also, the efficacy of liposomal doxorubicin is significantly enhanced via the downregulation of CD73 ectonucleotidase.
Preclinical • Journal
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EGFR (Epidermal growth factor receptor) • CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • NT5E (5'-Nucleotidase Ecto) • FOXP3 (Forkhead Box P3)
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CD73 expression
23d
Low expression of PGC-1β and other mitochondrial biogenesis modulators in melanoma is associated with growth arrest and the induction of an immunosuppressive gene expression program dependent on MEK and IRF-1. (PubMed, Cancer Lett)
Using pharmacological and gene silencing approaches, we further show that MEK1/2 and IRF-1 mediate the observed immune transcriptional response. Overall, this research suggests that mitochondrial biogenesis modulators can modulate tumor progression, immune evasion, and response to therapeutics through transcriptional control of immune pathways.
Journal • IO biomarker
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MAP2K1 (Mitogen-activated protein kinase kinase 1) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • PD-L2 (Programmed Cell Death 1 Ligand 2) • IRF1 (Interferon Regulatory Factor 1) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • IL1B (Interleukin 1, beta) • HSPA9 (Heat Shock Protein Family A (Hsp70) Member ) • LGALS9 (Galectin 9)
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IRF1 expression • CD73 expression
23d
The anticancer effects of cyanidin 3-O-glucoside combined with 5-fluorouracil on lung large-cell carcinoma in nude mice. (PubMed, Biomed Pharmacother)
This in vivo study demonstrated that C3G alone or combined with 5-FU may impair the growth of lung LCC and inhibit tumorigenesis. The findings indicate that C3G alone or C3G combined with 5-FU may be beneficial for treating human lung LCC.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CD44 • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • IL1B (Interleukin 1, beta) • CRP (C-reactive protein)
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CD73 expression
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5-fluorouracil
23d
Proteomics Study of Mesenchymal Stem Cell-Like Cells Obtained from Tumor Microenvironment of Patients with Malignant and Benign Salivary Gland Tumors. (PubMed, Cell J)
Malignant and benign SGTs probably exhibit a distinct pattern of tissue proteins that are most likely related to the metabolic pathway. However, further studies in a large number of patients are required to determine the applicability of identified proteins as new targets for cancer therapy.
Journal
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CD44 • CD34 (CD34 molecule) • CD133 • CD14 • CD24 (CD24 Molecule) • KRT7 (Keratin-7) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • THY1 (Thy-1 membrane glycoprotein) • ENG (Endoglin) • FKBP5 (FKBP Prolyl Isomerase 5) • HSPA4 (Heat Shock Protein Family A (Hsp70) Member 4)
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CD73 expression • CD133 expression • CD14 expression • CD24 expression
24d
CD73 facilitates invadopodia formation and boosts malignancy of head and neck squamous cell carcinoma via the MAPK signaling pathway. (PubMed, Cancer Sci)
As expected, knockdown of CD73 inhibited the MAPK signaling pathway, and the suppressive effect of CD73 knockdown on proliferation, migration, invasion and invadopolia formation was reversed by a MAPK signaling activator. Our results suggest that CD73 could promote the proliferation, migration, invasion and invadopodia formation of HNSCC via the MAPK signaling pathway and provide new mechanistic insights into the nonimmunological role of CD73 in HNSCC.
Journal
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NT5E (5'-Nucleotidase Ecto)
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CD73 overexpression • CD73 expression • NT5E overexpression
1m
The Effects of CD73 on Gastrointestinal Cancer Progression and Treatment. (PubMed, J Oncol)
Solving the problem of immunosuppression in GI cancer is the key to developing an effective therapeutic option and the modulation of CD73 expression may provide an answer. In this review, we discuss current research on CD73 in gastric, liver, pancreatic, and colorectal cancer to evaluate its therapeutic potential as an immunotherapy target in GI cancers.
Review • Journal • IO biomarker
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NT5E (5'-Nucleotidase Ecto)
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CD73 expression
1m
Functional expression of CD73 on human natural killer cells. (PubMed, Cancer Immunol Immunother)
In addition, glioblastoma patient data show that tumor-infiltrating NK cells express CD73 variably, depending on donor, and present lower expression of CD16, alongside patient-specific changes in CEACAM1, CXCR3 and TIM-3, suggesting some functional changes in NK cell responses associated with expression of CD73 on NK cells in vivo. Taken together, our study is the first to show that while NK cells are largely resistant to the upregulation of CD73, CD73 expression is inducible on NK cells in response to CD73 on cancer cells, and these cells are associated with distinct functional signatures.
Journal • IO biomarker
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HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CEACAM1 (CEA Cell Adhesion Molecule 1) • CXCR3 (C-X-C Motif Chemokine Receptor 3) • NT5E (5'-Nucleotidase Ecto)
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CD73 overexpression • CD73 expression • NT5E overexpression
1m
NT5E gene and CD38 protein as potential prognostic biomarkers for childhood B-acute lymphoblastic leukemia. (PubMed, Purinergic Signal)
Noteworthy, we observed higher CD38 expression on WBC than blasts in MRD > 0.1% patients. We suggest that NT5E gene and CD38 protein expression, of the ectonucleotidases family, could provide interesting prognostic biomarkers for childhood B-ALL.
Journal • IO biomarker
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CD38 (CD38 Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto) • DPP4 (Dipeptidyl Peptidase 4)
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CD38 expression • CD73 expression • NT5E overexpression
1m
Expression of CD73 on leukemic blasts increases during follow-up - a promising candidate marker for minimal residual disease detection in pediatric B-cell precursor acute lymphoblastic leukemia. (PubMed, Cent Eur J Immunol)
In 17 (9.6%) patients no change in expression of CD73 between diagnosis and day 15 of treatment was observed. In the great majority of cases the expression of CD73 is not only stable but increases during the early stages of treatment, which makes it a very useful marker to be used for MRD monitoring in childhood B-cell precursor (BCP)-ALL patients.
Journal • Minimal residual disease
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NT5E (5'-Nucleotidase Ecto)
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CD73 expression
1m
CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche. (PubMed, Int J Mol Sci)
Finally, we proved the efficacy of anti-CD73 agents in blocking NSCLC cell migration. Overall, we assessed the importance of adenosinergic signaling in the interaction between CSCs and OCs at the pre-metastatic niche, with therapeutic implications related to Ado production.
Journal
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CXCR4 (Chemokine (C-X-C motif) receptor 4) • CD133
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CD38 expression • CD73 expression
1m
Tumor Infiltration with CD20CD73 B Cells Correlates with Better Outcome in Colorectal Cancer. (PubMed, Int J Mol Sci)
Finally, neoadjuvant therapy correlated with reduced CD73 B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73 B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.
Journal • IO biomarker
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NT5E (5'-Nucleotidase Ecto)
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CD73 expression
2ms
CLINICAL SIGNIFICANCE OF CD73+ TUMOR INFILTRATING LYMPHOCYTES IN BREAST CANCER (GBCC 2022)
CD73+ TIL shows high expression in HR(-), HER2(+) breast cancer, and has different prognostic effects depending on breast cancer subtype.
Clinical • Tumor-Infiltrating Lymphocyte
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • ADAR (Adenosine Deaminase RNA Specific) • NT5E (5'-Nucleotidase Ecto)
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HER-2 positive • HER-2 expression • ER negative • CD73 expression • PGR negative
2ms
Exosomal CD73 from serum of patients with melanoma suppresses lymphocyte functions and is associated with therapy resistance to anti-PD-1 agents. (PubMed, J Immunother Cancer)
CD73 expressed on exosomes from serum of patients with melanoma produces adenosine and contributes to suppress T-cell functions. Early on-treatment, elevated expression levels of exosomal CD73 might affect the response to anti-PD-1 agents in patients with melanoma who failed to respond to therapy.
Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker
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IFNG (Interferon, gamma) • GZMB (Granzyme B) • NT5E (5'-Nucleotidase Ecto)
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PD-L1 expression • CD73 expression
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Keytruda (pembrolizumab) • Opdivo (nivolumab)
2ms
CD39 is highly expressed with TIGIT by CD8+ and regulatory CD4+ tumor infiltrating T cells in ovarian cancer (CIMT 2022)
We are currently expanding these experiments using primary mononuclear cells and combine the blockade of CD39 with that of TIGIT. Our current findings suggest that the immunosuppressive molecules TIGIT and CD39 represent additional potential targets to improve T-cell mediated cytotoxicity in OvCa patients.
IO biomarker
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CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • IL7R (Interleukin 7 Receptor) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD4 (CD4 Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • FOXP3 (Forkhead Box P3)
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CD8 expression • IL2RA expression • CD73 expression
2ms
The Prognostic Role of CD73/A2AR Expression and Tumor Immune Response in Periampullary Carcinoma Subtypes. (PubMed, Asian Pac J Cancer Prev)
PDAC and AC shared CD73 Overexpression while A2AR was overexpressed in PDAC only. In PDAC, CD73 and A2AR showed an opposed  prognostic effect but both had no prognostic impact on AC. In addition, tumor immune response showed a controversial impact on the prognosis of PDAC and AC.
Journal
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ADORA2A (Adenosine A2a Receptor)
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CD73 overexpression • CD73 expression • NT5E overexpression
2ms
Engineered Induced Pluripotent Stem Cell-derived Natural Killer Cells Reactively Co-target TIGIT and CD73 in the Glioblastoma Tumor Microenvironment (ASGCT 2022)
iPSC-NK cells can functionally express the construct upon maturation and expansion and can mediate powerful anti-tumor functions against patient-derived GBM models in vitro and in vivo. Such locally-activated iPSC-NK cells are able to specifically target the local GBM TME while sparing healthy tissues, promote restored NK cell metabolism and drive TIGIT signaling away from immunosuppression.Overall, co-targeting CD155 and CD73 in a localized, responsive manner can dampen immunosuppression and significantly enhance the killing potential of engineered iPSC­-NK cells against aggressive patient-derived GBM tumors as a programmable, off-the-shelf immunotherapy.
TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • PVR (PVR Cell Adhesion Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
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CD73 overexpression • CD73 expression
2ms
A Novel Anti-CD73 Antibody That Selectively Inhibits Membrane CD73 Shows Antitumor Activity and Induces Tumor Immune Escape. (PubMed, Biomedicines)
Intriguingly, in a xenograft mouse model of acute lymphocytic leukemia (ALL), 22E6 treatment resulted in an initial tumor growth delay in some animals, followed by a complete loss of CD73 expression on ALL cells in all 22E6 treated animals, indicating tumor immune escape. Taken together, 22E6 shows great potential for cancer therapy, favorably in combination with other drugs.
Journal
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NT5E (5'-Nucleotidase Ecto)
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CD73 expression
2ms
New P2 trial • Combination therapy
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PD-L1 (Programmed death ligand 1) • CD276 (CD276 Molecule)
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PD-L1 expression • CD73 expression
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Keytruda (pembrolizumab) • enoblituzumab (MGA271)
2ms
Transcriptome analysis of tumor-derived mesenchymal progenitor cells shows that CHST15 is a fibrosis regulator of retroperitoneal liposarcoma. (PubMed, Ann Transl Med)
CHST15 is upregulated in tumor-derived MPCs and regulates fibrosis in RPLS. This provides clues for development of novel therapeutic strategies by targeting CHST15-induced MPC activation in RPLS.
Journal
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FGF2 (Fibroblast Growth Factor 2) • THY1 (Thy-1 membrane glycoprotein) • ENG (Endoglin) • NT5E (5'-Nucleotidase Ecto)
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CD73 expression
3ms
Genetic characteristics involving the PD-1/PD-L1/L2 and CD73/A2aR axes and the immunosuppressive microenvironment in DLBCL. (PubMed, J Immunother Cancer)
This study describes the additional genetic basis of PD-L1 overexpression and characterizes certain genetic alterations of CD73/A2aR in DLBCL. The degree of T-cell dysfunction is correlated with clinical outcomes. Strategies that reverse T-cell dysfunction by inhibiting PD-1/PD-L1/L2, particularly in combination with CD73/A2aR, may show potential as effective therapeutic options for DLBCL.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • PD-L2 (Programmed Cell Death 1 Ligand 2) • NT5E (5'-Nucleotidase Ecto)
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PD-L1 overexpression • CD73 expression
3ms
Identification and validation of ecto-5' nucleotidase as an immunotherapeutic target in multiple myeloma. (PubMed, Blood Cancer J)
Combination of anti-CD73 Abs and an immune-stimulating agent TLR-7 agonist enhances autologous MM-specific CD8 CTL activity. Taken together, our preclinical data suggest that the therapeutic targeting of CD73, alone or in combination with TLR-7 agonist, represents a promising novel strategy to restore host anti-MM immunity.
Journal • IO biomarker
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CD8 (cluster of differentiation 8)
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CD73 expression
3ms
Role of CD73 on peritoneal macrophages in age-associated immune dysfunction and tumor immunity (IMMUNOLOGY 2022)
In ongoing experiments, we are utilizing conditional deletion approaches to address the role of CD73 specifically on macrophages in these models. Results from this study will provide insight into the immunoregulatory role of CD73 on TRM during aging and cancer, and will help refine therapeutic approaches targeting CD73 in cancer immunotherapy.
IO biomarker
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TNFA (Tumor Necrosis Factor-Alpha)
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CD73 expression
3ms
Anti-PD-L1 and anti-CD73 combination therapy promotes T cell response to EGFR-mutated NSCLC. (PubMed, JCI Insight)
Consistently, there were increases in gene expression that corresponded to inflammation and T cell function in tumors treated with the combination of anti-PD-L1 and anti-CD73. Together, these results further support the combination of anti-CD73 and anti-PD-L1 therapies in treating EGFR-mutated NSCLC, while suggesting that increased T cell activity may play a role in response to therapy.
Journal • Combination therapy • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • NT5E (5'-Nucleotidase Ecto)
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EGFR mutation • EGFR wild-type • CD73 expression
4ms
Altered mucosal immune-microbiota interactions in familial adenomatous polyposis. (PubMed, Clin Transl Gastroenterol)
Loss of resident memory T-cells and γδ T-cells in mucosal tissue of patients with FAP accompanies intestinal microbial dysbiosis previously reported in this pre-cancerous state and suggests impaired cellular immunity and tumor surveillance. This may lead to barrier dysfunction, possible loss of regulatory T-cell function and excess IgA antibody secretion. Our data are the first to implicate mucosal immune dysfunction as a contributing factor in this genetically driven disease and identify potentially critical pathways in the etiology of CRC.
Journal
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CD8 (cluster of differentiation 8) • APC (APC Regulator Of WNT Signaling Pathway) • CD4 (CD4 Molecule) • ITGAE (Integrin Subunit Alpha E) • NT5E (5'-Nucleotidase Ecto)
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CD8 expression • CD73 expression
4ms
Expression Profiles of Immune Cells after Propofol or Sevoflurane Anesthesia for Colorectal Cancer Surgery: A Prospective Double-blind Randomized Trial. (PubMed, Anesthesiology)
Propofol-based anesthesia was not superior to sevoflurane-based anesthesia in terms of alleviating suppression of immune cells including natural killer cells and T lymphocytes during colorectal cancer surgery.
Clinical • Journal
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ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
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CD73 expression
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sevoflurane
4ms
Reshaping the myeloid-dependent pro-tumorigenic microenvironment in PDAC by targeting the extracellular adenosine pathway: A therapeutic opportunity (AACR 2022)
Blocking the in vivo formation and function of eAdo in IOTResi tumors, using a combination of anti-CD73 antibody (2C5, murine IgG1-Fc) and an inhibitor of Adora2a (AZD4635) reduced the presence of eAdo, slowed tumor growth and reduced the lung metastatic burden. In addition, blocking the adenosine pathway improved the efficacy of combinations of cytotoxics (gemcitabine/ATR inhibitor) and immunotherapy (aCD40/anti-PDL1Ab).The formation of eAdo appears to be a factor in the development of the immunosuppressive TME in PDAC, contributing to its resistance to conventional and novel therapies. Therefore, inhibition of the adenosine pathway using a CD73Ab and an Adora2ai may represent a strategy to modulate the PDAC stroma and improve therapy response in patients with PDAC.
Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • ADORA2A (Adenosine A2a Receptor) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
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PD-L1 expression • TMB-L • CD73 expression
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gemcitabine • imaradenant (AZD4635)
4ms
Targeting CD73 augments the efficacy of A2aR blockade in PTEN-deficient prostate cancer (AACR 2022)
The efficacy of AZD4635 versus aCD73 plus AZD4635 was evaluated in an in vivo castration-sensitive model of Pten-null prostate cancer treated with apalutamide plus androgen deprivation therapy via surgical castration. Moreover 75% (6/8) of mice treated with aCD73/AZD4635 had tumor burden reductions greater than 30% relative to vehicle treated controls versus 28.6% (2/7) of mice in the AZD4635 only group. Our findings show that extracellular adenosine is a key immunosuppressive molecule in PTEN-deficient prostate cancer and provide evidence that implicates adenosinergic signaling via CD73 as a contributing factor to decreased efficacy of A2aR blockade and progression to CRPC.
Clinical
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PTEN (Phosphatase and tensin homolog) • GZMB (Granzyme B) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
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CD73 expression
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Erleada (apalutamide) • imaradenant (AZD4635)
4ms
A novel therapeutic antibody against CD73 that ameliorates the tumor microenvironment and improves the efficacy of cancer immunotherapy (AACR 2022)
The novel anti-human CD73 antibody, BP1200, ameliorates immunosuppressive TME caused by adenosine and enhances antitumor immune responses. The combination of BP1200 and immune-checkpoint inhibitors for cancer treatment will be a promising therapeutic option in clinical practice.
Clinical • PD(L)-1 Biomarker • IO biomarker
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NT5E (5'-Nucleotidase Ecto)
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CD73 expression
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BP1200
4ms
ORIC-533, a small molecule CD73 inhibitor with best-in-class properties, reversesimmunosuppression and has potential as an immunomodulatory therapy in patients with multiple myeloma (AACR 2022)
Recent clinical proof of concept data demonstrated a significant improvement in progression free survival for non-small cell lung cancer patients upon targeting CD73 with the oleclumab anti-CD73 antibody in combination with anti-PDL1, relative to anti-PDL1 checkpoint inhibitor treatment alone.We developed ORIC-533, a potent, orally bioavailable, AMP-competitive, small molecule inhibitor of CD73, that is highly selective for CD73 and exhibits picomolar potency in biochemical assays, completely blocking adenosine production from AMP. Taken together, these results demonstrate that the ORIC CD73 inhibitor potently inhibits the adenosine pathway, which restores anti-tumor immunity and therefore holds potential for patients with MM. Based upon these data, ORIC-533 is being studied as a single agent in a Phase 1 clinical trial in patients with relapsed or refractory multiple myeloma.
Clinical • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8)
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CD73 overexpression • CD73 expression • NT5E overexpression
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oleclumab (MEDI9447) • ORIC-533
4ms
Novel orthotopic pancreatic cancer cell lines derived from B6-KPC mice (AACR 2022)
Moreover, Gemcitabine or combined with CD40 agonist presented significant tumor growth inhibition in B6 bearing mPAKPC-Luciferase orthotopic mouse models...In addition, the immune profiling of this cell line showed highly expressed of potential therapeutic targets, including Claudin 18.2, CD47, CD73. Thus, mPAKPC-Luciferase cell lines are valuable models for the PDAC preclinical therapies.
Preclinical • PD(L)-1 Biomarker • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CLDN18 (Claudin 18) • CD40 (CD40 Molecule) • PDX1 (Pancreatic And Duodenal Homeobox 1)
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KRAS G12D • KRAS G12 • CD73 expression
|
gemcitabine
4ms
Metabolic engineering of CAR-T cells overcomes suppressive adenosine signaling and enhances functionality (AACR 2022)
Further, ectopic overexpression of adenosine deaminase (ADA) in CAR T cells led to decreased exhaustion marker expression and significantly enhanced effector function. These data indicate that ADA overexpression is an innovative approach to increase the functionality of CAR T cells through avoidance of suppressive adenosine signaling, and provides proof-of-concept that metabolic engineering of CAR-T cells can pave the way for responses in patients with solid tumors.
CAR T-Cell Therapy • IO biomarker
|
CD19 (CD19 Molecule) • ADORA2A (Adenosine A2a Receptor) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
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CD73 expression
4ms
CD73 induces GM-CSF/MDSC-mediated suppression of T cells to accelerate pancreatic cancer pathogenesis. (PubMed, Oncogene)
Finally, anti-CD73 antibody treatment significantly improved gemcitabine efficacy in orthotopic models. Thus, targeting the adenosine axis presents a novel therapeutic opportunity for improving the anti-tumoral immune response against PDAC.
Journal • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule) • CSF2 (Colony stimulating factor 2) • NT5E (5'-Nucleotidase Ecto)
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IFNG expression • CD73 expression
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gemcitabine
5ms
Amplification of spatially isolated adenosine pathway by tumor-macrophage interaction induces anti-PD1 resistance in hepatocellular carcinoma. (PubMed, J Hematol Oncol)
In summary, HCC-derived exosomal circTMEM181 contributes to immunosuppression and anti-PD1 resistance by elevating CD39 expression, and inhibiting the ATP-adenosine pathway by targeting CD39 on macrophages can rescue anti-PD1 therapy resistance in HCC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
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CD73 expression
6ms
Enrollment closed • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • NT5E (5'-Nucleotidase Ecto)
|
PD-L1 expression • HER-2 positive • HR positive • HER-2 negative • ER negative • CD73 expression
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carboplatin • Imfinzi (durvalumab) • paclitaxel • oleclumab (MEDI9447)
6ms
Prognostic implications of adaptive immune features in MMR-proficient colorectal liver metastases classified by histopathological growth patterns. (PubMed, Br J Cancer)
Combining the assessments of HGP and adaptive immune features in resected CRLM could help identify patients at risk of early recurrence.
Journal
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
7ms
CD73-Mediated Immunosuppression Is Linked to a Specific Fibroblast Population That Paves the Way for New Therapy in Breast Cancer. (PubMed, Cancers (Basel))
Our data support the potential clinical benefit of using both anti-CD73 and immune-checkpoint inhibitors in breast cancer patients for inhibiting CAF-S1-mediated immunosuppression and enhancing anti-tumor immune response.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • NT5E (5'-Nucleotidase Ecto)
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CD73 expression
7ms
The enhanced cell cycle related to the response to adjuvant therapy in pancreatic ductal adenocarcinoma. (PubMed, Genomics)
In conclusion, this study showed that patients characterized as ECC-high not only had reduced RFS and OS rates, but were also more sensitive to adjuvant chemotherapy and could potentially be less sensitive to immune checkpoint inhibitors. Being able to characterize patients by these parameters would allow doctors to make more informed decisions on patient treatment regimens.
Clinical • Journal • IO biomarker
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CD8 (cluster of differentiation 8) • NT5E (5'-Nucleotidase Ecto)
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CD73 expression
7ms
CD73 Severed as a Potential Prognostic Marker and Promote Lung Cancer Cells Migration via Enhancing EMT Progression. (PubMed, Front Genet)
CD73 play an important role in LUAD cells proliferation and migration. These data allowed to support CD73 as a therapeutic target for LUAD.
Journal
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 overexpression • CD73 expression • NT5E overexpression
7ms
Silencing tumor-intrinsic CD73 enhances the chemosensitivity of NSCLC and potentiates the anti-tumoral effects of cisplatin: An in vitro study. (PubMed, Biomed Pharmacother)
Besides suppressing anti-tumoral immune responses, tumor-intrinsic CD73 can facilitate NSCLC development, and the combined cisplatin therapy with CD73-siRNA transfection can substantially enhance the chemosensitivity of NSCLC to cisplatin and potentiates cisplatin-induced anti-tumoral effects on NSCLC.
Preclinical • Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CASP3 (Caspase 3) • MMP9 (Matrix metallopeptidase 9)
|
MYC expression • CD73 expression
|
cisplatin
7ms
Clinicopathologic correlates and prognostic relevance of the immune checkpoint CD73 (NT5E) in resected biliary cancers (BC). (ASCO-GI 2022)
In this study, we provided a clinicopathologic characterization of CD73 expression in resected BC, demonstrating that tCD73 is an independent negative prognostic biomarker in this disease. Although these findings are in need of a validation in larger dataset, they foster novel combination of anti-CD73 agents with conventional therapy in the poorer-prognosis subset of CD73-positive BC.
Clinical
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
7ms
Impact of intratumoural CD73 expression on prognosis and therapeutic response in patients with gastric cancer. (PubMed, Eur J Cancer)
High CD73 expression indicated an immunoevasive contexture with CD8+ T cell dysfunction and represented an independent predictor for adverse clinical outcomes. As a potential immunotherapeutic target, CD73 could potentially be a novel biomarker for adjuvant chemotherapy, targeted therapies and immunotherapy. The crucial role of CD73 in the therapeutic landscape of GC needs further validation retrospectively and prospectively.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
FGFR2 (Fibroblast growth factor receptor 2) • CD8 (cluster of differentiation 8) • NT5E (5'-Nucleotidase Ecto)
|
CD73 overexpression • CD73 expression • NT5E overexpression
|
Keytruda (pembrolizumab) • 5-fluorouracil
8ms
Multiplex single-cell analysis of cancer cells enables unbiased uncovering subsets associated with cancer relapse: heterogeneity of multidrug resistance in precursor B-ALL. (PubMed, ChemMedChem)
Our data provide the first evidence that highly expressed multidrug resistance biomarkers in certain cell subpopulations with specific immunophenotypes may potentially induce B-ALL recurrence. The incorporation of multidrug resistance features with cell phenotypes using mass cytometry proposed in this study provides a general strategy for risk assessment and the prediction of recurrence of different types of cancers.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • CD38 (CD38 Molecule) • CD34 (CD34 molecule) • MME (Membrane Metalloendopeptidase) • NRP1 (Neuropilin 1) • NT5E (5'-Nucleotidase Ecto)
|
CD73 overexpression • CD73 expression
8ms
Prognostic significance of NT5E/CD73 in neuroblastoma and its function in CSC stemness maintenance. (PubMed, Cell Biol Toxicol)
Overexpressing CD73 in CHLA-20 and CHLA-90 cells with low CD73 and silencing in CHLA-171 and CHLA-172 cells with high CD73 showed that CD73 regulates epithelial to mesenchymal transition (E-Cadherin, N-Cadherin, Vimentin), stemness maintenance (Sox2, Nanog, Oct3/4), self-renewal capacity (Notch), and differentiation inhibition (leukemia inhibitory factor, LIF) proteins (confocal-immunofluorescence). These results demonstrate that high CD73 can predict good prognosis in NB, and further suggest that CD73 regulates stemness maintenance in cells that defy clinical therapy.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDH1 (Cadherin 1) • SOX2 • VIM (Vimentin) • NANOG (Nanog Homeobox) • NT5E (5'-Nucleotidase Ecto)
|
CD73 overexpression • CD73 expression • NT5E overexpression
8ms
Oct4/Sox2 drive an immunosuppressive GSC phenotype by inducing T-reg effector genes via TGFBR2 signaling (SNO 2021)
Taken together, we show that reprogramming events initiated by Oct4 and Sox2 induce a CD44 + /FOX3P - GSC cell subset with a T-reg-like immunosuppressive transcriptional profile via a TGFBR2-dependent mechanism. This research provides the first description of such neoplastic cells in any malignancy and has high potential translational impact since targeting these tumor cell subsets and their immunosuppressive mechanisms may be critical to the successful development of GBM immunotherapies.
PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD44 • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • POU5F1 (POU Class 5 Homeobox 1) • SOX2 • TGFB1 (Transforming Growth Factor Beta 1) • LGALS1 (Galectin 1) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • FOXP3 (Forkhead Box P3)
|
CD73 expression • POU5F1 expression
8ms
CD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion. (PubMed, Cell Death Dis)
In vivo, defects in exosomal synthesis and CD73 expression significantly inhibited tumour growth in GBM tumour-bearing mice and restored the clonal proliferation of T cells in the central and peripheral regions. These data indicate that CD73+ TDEVs can be used as a potential target for GBM immunotherapy.
Journal • IO biomarker
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
8ms
Deep Phenotyping Reveals Expansion of T Follicular Regulatory Cells and Triple Positive (CTLA4, TIGIT, PD1) Exhausted Effector Memory T Cells Characterizing the Immunosuppressive Microenvironment in Follicular Lymphoma (ASH 2021)
In addition, the noteworthy expansion of TIM3+ memory CD8 cells in FL. Targeting these most highly expressed checkpoints in FL alone or in combination may provide an avenue for rational trial design.
PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • IL2RA (Interleukin 2 receptor, alpha) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • FOXP3 (Forkhead Box P3) • CXCR5 (C-X-C Motif Chemokine Receptor 5)
|
CD8 expression • PD-1 expression • HAVCR2 expression • LAG3 expression • CD73 expression • CTLA4 expression
8ms
CD73 Inhibition Overcomes Immunosuppression and Triggers Autologous T-Cell Mediated Multiple Myeloma Cell Lysis in the Bone Marrow Milieu (ASH 2021)
This study therefore demonstrates that: 1. CD73-mediated adenosine activity suppresses the cytolytic activity of T-cells against tumor cells in the MM BM milieu; and 2. CD73 inhibition can overcome immune suppression and restore lysis of MM cells by autologous T-cells.
IO biomarker
|
CD8 (cluster of differentiation 8) • CD69 (CD69 Molecule) • CD40 (CD40 Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto) • CD86 (CD86 Molecule)
|
CD73 overexpression • CD73 expression • NT5E overexpression
|
ORIC-533
8ms
[VIRTUAL] Radiation, Adenosine Signaling, and Immunosuppressive Changes to the Tumor Microenvironment (ASTRO 2021)
Radiation induces an immunosuppressive TME, increasing the abundance of PMN-MDSCs and M-MDSCs and activating adenosine signaling. Radiation increases the expression of adenosine receptors on CD45+ TILs at the transcriptomic level and cell surface expression of CD73 on monocytes and A2AR on granulocytes. Treatment of human PBMCs with adenosine receptor agonist resulted in loss of effector T-cell function and suppressive changes to cytokine milieu.
CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • CCL2 (Chemokine (C-C motif) ligand 2) • GZMB (Granzyme B) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ITGAM (Integrin, alpha M) • NT5E (5'-Nucleotidase Ecto) • TRB (T Cell Receptor Beta Locus) • IFNB1 (Interferon Beta 1)
|
CD73 expression
8ms
Radiation, Adenosine Signaling, and Immunosuppressive Changes to the Tumor Microenvironment. (PubMed, Int J Radiat Oncol Biol Phys)
Radiation induces an immunosuppressive TME, increasing the abundance of PMN-MDSCs and M-MDSCs and activating adenosine signaling. Radiation increases the expression of adenosine receptors on CD45+ TILs at the transcriptomic level and cell surface expression of CD73 on monocytes and A2AR on granulocytes. Treatment of human PBMCs with adenosine receptor agonist resulted in loss of effector T-cell function and suppressive changes to cytokine milieu. These data suggest a mechanistic link between radiation, adenosine signaling and the myeloid compartment.
Journal
|
CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • CCL2 (Chemokine (C-C motif) ligand 2) • GZMB (Granzyme B) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ITGAM (Integrin, alpha M) • NT5E (5'-Nucleotidase Ecto) • TRB (T Cell Receptor Beta Locus) • IFNB1 (Interferon Beta 1)
|
CD73 expression
8ms
Immune related endonucleases and GTPases are not associated with tumor response in patients with advanced non-small cell lung cancer treated with checkpoint inhibitors. (PubMed, Pathol Res Pract)
Separate and combined expression of 5 biomarkers involved in the immune response (CD73, CD39, VISTA, Arl4d, and Cytohesin-3) was not associated with response in our cohort of advanced NSCLC patients receiving single agent ICI. To confirm our findings the analysis of independent larger cohorts is warranted.
Clinical • Journal • Checkpoint inhibition • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • KEAP1 (Kelch Like ECH Associated Protein 1) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
PD-L1 expression • STK11 mutation • ARID1A mutation • KEAP1 mutation • CD73 expression
8ms
CD73 is a hypoxia-responsive gene and promotes the Warburg effect of human gastric cancer cells dependent on its enzyme activity. (PubMed, J Cancer)
By the subcutaneous xenograft model, we confirmed the promotive roles of CD73 in regulating cell proliferation and glycolysis in gastric cancer. This study provides strong evidence of the involvement of CD73 in the Warburg effect and indicates that it could be a novel antitumor strategy to target tumor metabolism in gastric cancer.
Journal
|
CD73 overexpression • CD73 expression • NT5E overexpression
9ms
Results of NSGO-OV-UMB1/ENGOT-OV30 study: A phase II study of durvalumab and oleclumab in patients with relapsed ovarian cancer (OC) (ESGO 2021)
Conclusion* Combination of Oleclumab-durvalumab is feasible and demonstrate modest preliminary activity in relapsed OC. Further biomarker analysis research to predict response is ongoing.
Clinical • P2 data • Late-breaking abstract • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • NT5E (5'-Nucleotidase Ecto)
|
PD-L1 expression • CD8 expression • CD8 positive • CD73 expression
|
Imfinzi (durvalumab) • oleclumab (MEDI9447)
9ms
A novel circular RNA circ_HN1/miR-628-5p/Ecto-5'-nucleotidase competing endogenous RNA network regulates gastric cancer development. (PubMed, Bioengineered)
Moreover, depletion of miR-628-5p reversed the effects of circ_HN1 silencing on regulating cell functional behaviors. Our findings identify a novel ceRNA network, the circ_HN1/miR-628-5p/NT5E axis, for the oncogenic activity of circ_HN1 in gastric cancer, highlighting circ_HN1 inhibition as a promising targeted treatment against gastric cancer.
Journal
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
9ms
[VIRTUAL] Immunophenotyping of tumor-infiltrating T cells in primary CNS lymphoma (EANO 2021)
Taken together, our study demonstrates a strong infiltration of cytotoxic CD8+ T cells into cerebral lymphoma, which potentially can be disinhibited using checkpoint immunotherapy. Our profiling suggests that PD-1 and TIGIT present appealing targets for such kind of immune disinhibition.
PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD4 (CD4 Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD8 expression • PD-1 expression • CD73 expression
9ms
Immunophenotypic characterization of NK cells in multiple myeloma (DGHO 2021)
Our analyzes discovered a characteristic phenotype of PD-1 + CD39 + CD47 + CD56dimCD16 + CD3- NK cells in the BM from patients with diagnosed MM. Based on these data, we are currently evaluating the functional role of the combinatorial inhibition of PD -1, CD39 and CD47 on NK-cell mediated cytotoxicity.
PD(L)-1 Biomarker • IO biomarker
|
CD47 (CD47 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
PD-1 expression • CD73 expression
9ms
TOX is a transcription factor associated with expression of PD-1 on CD8 + T cells in AML (DGHO 2021)
In summary, we could show that expression of TOX is associated with an aberrant cell population of PD-1 + TIGIT + CD73- CD8 + T cells in the PB and BM from patients with newly diagnosed AML. Based on these data, we are currently carrying out functional assays to evaluate the role of TOX in order to discover its potential as therapeutic target with regards to the boosting of antileukemic immune responses.
PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CCR7 (Chemokine (C-C motif) receptor 7)
|
CD8 expression • PD-1 expression • CD73 expression • CCR7 expresion
9ms
Engineered natural killer cells reactively block TIGIT and CD73 in the GBM microenvironment (SITC 2021)
Overall, cytolytic function of engineered NK cells against GBM was significantly higher than that of non-engineered NK cells, with or without CD73 (10 ug/mL) and TIGIT (50 ug/mL) antibodies, for E:T ratios of 5:1 and 10:1, demonstrating the functional efficacy of our genetic construct. Conclusions Overall, we have shown that co-targeting CD155 and CD73 in a localized, responsive manner can dampen immunosuppression and significantly enhance the killing potential of engineered NK cells against aggressive patient-derived GBM tumors.
IO biomarker
|
TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 overexpression • CD73 expression
9ms
Activating CD73 on B cells as a target for immunotherapy of COVID-19 and viral associated cancers: Clinical activity in human papilloma virus positive (HPV) head and neck squamous cell cancers (HNSCC) (SITC 2021)
Background Mupadolimab (mupa) is a humanized FcγR binding-deficient IgG1 anti-CD73 antibody that has agonistic properties.1 CD73 is involved in production of adenosine and in cellular trafficking...Cross blocking and cellular internalization studies showed that mupa is distinct from other anti-CD73 antibodies such as MEDI9447 and AD2...This activity supports a strategy to combine mupa with pembrolizumab to enhance both humoral and cellular immunity in the treatment of viral associated cancers such as HPV+HNSCC, and viral infections. Trial Registration NCT03454451
Clinical • PD(L)-1 Biomarker • IO biomarker
|
CD69 (CD69 Molecule) • SDC1 (Syndecan 1) • NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
|
Keytruda (pembrolizumab) • oleclumab (MEDI9447) • mupadolimab (CPI-006)
9ms
Increased frequency PD1 + TIGIT + CD73-V 1+ T cells in newly diagnosed ovarian cancer (DGHO 2021)
In summary, we could show that in MA from patients with newly diagnosed OC, an aberrant γδ T-cell population of PD1 + TIGIT + CD73 - Vδ1 + T-cells is prevalent in contrast to PB. Based on these data, we are currently carrying out functional assays to evaluate the role of TIGIT and PD1 on Vδ1 + T-cell function with regard to the boosting of anti-ovarian cancer immune responses.
PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD27 • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression
10ms
Plasmacytoid dendritic cells recruited by HIF-1α/eADO/ADORA1 signaling induce immunosuppression in hepatocellular carcinoma. (PubMed, Cancer Lett)
Depletion of pDCs using a monoclonal antibody or an ADORA1 antagonist significantly improved antitumor immunity and suppressed HCC growth in the immunocompetent HCC mouse model. Thus, targeting pDC recruitment may serve as a potential adjuvant strategy for immunotherapies in HCC.
Journal • IO biomarker
|
CD8 (cluster of differentiation 8) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression • HIF1A expression
10ms
circHMGCS1-016 reshapes immune environment by sponging miR-1236-3p to regulate CD73 and GAL-8 expression in intrahepatic cholangiocarcinoma. (PubMed, J Exp Clin Cancer Res)
CircHMGCS1-016 is a forceful contributor in ICC development and immune tolerance via miR-1236-3p/CD73 and GAL-8 axis. CircHMGCS1-016 can be explored as a new potential biomarker and therapeutic target for PD1-resistant ICC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8)
|
CD73 expression
10ms
CD73 Promotes Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma. (PubMed, Cancers (Basel))
In addition, we selected another cohort consisting of 38 ESCC patients receiving nivolumab or pembrolizumab and found that treatment response and survival benefit to immunotherapy were strongly correlated with the expression levels of CD73/programmed death ligand 1. The findings of our study indicate CD73 may be an independent prognostic factor for ESCC patients who underwent esophagectomy. Furthermore, it may be associated with the patient responses to immunotherapy.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CDH1 (Cadherin 1) • VIM (Vimentin) • NT5E (5'-Nucleotidase Ecto)
|
PD-L1 expression • CD73 overexpression • CD73 expression • NT5E overexpression • VIM expression
|
Keytruda (pembrolizumab) • Opdivo (nivolumab)
10ms
Breast Cancer Cell-Derived Adenosine Enhances Generation and Suppressor Function of Human Adaptive Regulatory T Cells. (PubMed, J Pers Med)
BrCa producing ADO (CD73+ TU) favor the induction of Tr1, which expresses CD39 and CD73, hydrolyzes ATP to ADO, and effectively suppresses anti-tumor immunity.
Journal • BRCA Biomarker
|
CD4 (CD4 Molecule) • ADORA2A (Adenosine A2a Receptor) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
10ms
[VIRTUAL] Preclinical Validation of Ecto-5’ Nucleotidase (NT5E/CD73) as a Novel Immunotherapeutic Target in Multiple Myeloma (IMW 2021)
Our preclinical data therefore suggest that the therapeutic targeting of CD73, alone or in combination with TLR7 agonist, represents a promising novel strategy to restore host anti-MM immunity.
Preclinical • IO biomarker
|
CD8 (cluster of differentiation 8) • CD40 (CD40 Molecule) • NT5E (5'-Nucleotidase Ecto) • CD86 (CD86 Molecule)
|
CD73 expression
10ms
CD73 expression in myeloid-derived suppressor cells is correlated with clinical stages in head and neck squamous cell carcinomas. (PubMed, Ann Transl Med)
These CD73 PMN-MDSCs contributes to T cell immune suppression activity in HNSCC patients. Using ectonucleotidase inhibitors is a promising rationale for PMN-MDSCs in future clinical development of immunotherapy in human HNSCC cancer.
Clinical • Journal • IO biomarker
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
11ms
Rat Adipose-Derived Stromal Cells (ADSCs) Increases the Glioblastoma Growth and Decreases the Animal Survival. (PubMed, Stem Cell Rev Rep)
These results indicate that the immunoregulatory properties of ADSCs and its contribution to tumor stroma can support tumor growth leading to larger zones of necrosis, recruitment of immune cells, thus facilitating tumor progression. Our data provide new insights into the way by which ADSCs and tumor cells interact and highlight the importance of understanding the fate and roles of MSCs in tumor sites in vivo, as well as their intricate crosstalk with cancer cells.
Preclinical • Journal
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
11ms
Arginase Pathway Markers of Immune-Microenvironment in Thymic Epithelial Tumors and Small Cell Lung Cancer. (PubMed, Clin Lung Cancer)
Arginase-1 was not detectable in TETs and SCLC. Expression of markers in the adenosine pathway were present in both TETs and SCLC. CD39 expression in tumor cells may identify subsets of patients with TETs with an unfavorable prognosis.
Journal • IO biomarker
|
PD-L2 (Programmed Cell Death 1 Ligand 2) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • FUT4 (Fucosyltransferase 4)
|
CD73 expression
11ms
High CD39 expression is associated with the non-muscle-invasive phenotype of human bladder cancer. (PubMed, Oncotarget)
The altered expression of CD39 presented herein supports the idea that this ectonucleotidase may be involved in bladder tumorigenesis. High expression of CD39 in tumor cells is correlated with the early stage of BC.
Journal
|
ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
11ms
CD28 engagement inhibits CD73-mediated regulatory activity of CD8 T cells. (PubMed, Commun Biol)
Our data support the notion that CD28 costimulation inhibits CD73 upregulation and thereby prevents CD8 T cells from becoming suppressive. This study uncovers a previously unidentified role for CD28 costimulation in CD8 T cell activation and suggests that the CD28 costimulatory pathway can be a potential target for cancer immunotherapy.
Journal • IO biomarker
|
CD8 (cluster of differentiation 8) • NT5E (5'-Nucleotidase Ecto)
|
CD8 expression • CD73 expression
11ms
CD73 expression in normal, hyperplastic, and neoplastic thyroid: a systematic evaluation revealing CD73 overexpression as a feature of papillary carcinomas. (PubMed, Virchows Arch)
These results were corroborated by NT5E mRNA profiling. Papillary carcinomas feature enhanced CD73 protein and mRNA expression with distinct and intense staining, more pronounced in the invasive fronts of the tumors.
Journal
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 overexpression • CD73 expression • NT5E overexpression
11ms
T cells drive negative feedback mechanisms in cancer associated fibroblasts, promoting expression of co-inhibitory ligands, CD73 and IL-27 in non-small cell lung cancer. (PubMed, Oncoimmunology)
In turn CAFs upregulate co-inhibitory receptors on T cells including the ectonucleotidase CD39 promoting development of an exhausted but highly cytotoxic phenotype. Our results highlight the bidirectional interaction between T cells and CAFs in promoting components of the immunosuppressive CD39, CD73 adenosine pathway and demonstrate IL-27 production can be induced in CAF by activated T cells.
Journal
|
IL6 (Interleukin 6) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression
11ms
CD73 induces gemcitabine resistance in pancreatic ductal adenocarcinoma: A promising target with non-canonical mechanisms. (PubMed, Cancer Lett)
The administration of TGZ markedly enhances sensitivity to GEM via downregulating CD73 in PDAC. Our findings support that CD73 could be targeted to overcome chemoresistance in PDAC.
Journal
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
|
gemcitabine
12ms
Single-cell RNA sequencing reveals distinct cellular factors for response to immunotherapy targeting CD73 and PD-1 in colorectal cancer. (PubMed, J Immunother Cancer)
The intratumoral immunomodulation of CD73 inhibition is distinct from PD-1 inhibition and exhibits potential as a novel anticancer immunotherapy for CRC, possibly through a synergistic effect when combined with PD-1 blocker treatments. This study may contribute to the ongoing development of anticancer immunotherapies targeting refractory CRC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • MALAT1 (Metastasis associated lung adenocarcinoma transcript 1) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tecentriq (atezolizumab) • quemliclustat (AB680)
12ms
High-dimensional and single-cell transcriptome analysis of the tumor microenvironment in angioimmunoblastic T cell lymphoma (AITL). (PubMed, Leukemia)
Notably, we find that B cells within the AITL TME feature decreased expression of key markers including CD73 and CXCR5. Furthermore, we describe the expansion of distinct CD8+ T cell populations that feature an exhausted phenotype and an underlying expression profile indicative of dysfunction, impaired cytotoxicity, and upregulation of the chemokines XCL2 and XCL1.
Journal
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CXCR5 (C-X-C Motif Chemokine Receptor 5)
|
CD73 expression
1year
Sustained compensatory p38 MAPK signaling following treatment with MAPK inhibitors induces the immunosuppressive protein CD73 in cancer: combined targeting could improve outcomes. (PubMed, Mol Oncol)
We show that high CD73 expression significantly correlates with worse outcome in MAPKi-treated colorectal cancer patients, highlighting the potential clinical importance of increased CD73 expression following MAPKi treatment. Our findings may explain the diminished effect of MAPKi in cancer patients and provides further rationale for combined anti-CD73 and MAPKi treatment.
Journal
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
1year
New insights into cytotoxic mechanisms of bozepinib against glioblastoma. (PubMed, Eur J Pharm Sci)
However, after another treatment round, the resistant cells were eliminated. Altogether, BZP presented in vitro anti-glioma activity, encouraging further in vivo studies in order to better understand its mechanism of action.
Journal
|
CD133 • CASP3 (Caspase 3) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression • CD133 expression
1year
Development and validation of an individualized immune prognostic model in stage I-III lung squamous cell carcinoma. (PubMed, Sci Rep)
The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I-III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.
Clinical • Journal • Tumor Mutational Burden • IO biomarker
|
TMB (Tumor Mutational Burden) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD47 (CD47 Molecule)
|
TMB-H • TMB-L • HAVCR2 expression • CD73 expression
1year
High level of CD73 predicts poor prognosis of intrahepatic cholangiocarcinoma. (PubMed, J Cancer)
Notably, the overexpression of CD73 or low tumour-infiltrating CD8 T cells was an independent indicator for predicting the OS and DFS of ICC patients. We revealed that CD73 expression and low tumour-infiltrating CD8T cells are valuable predictors of survival and recurrence in patients with ICC.
Journal
|
CD8 (cluster of differentiation 8) • NT5E (5'-Nucleotidase Ecto)
|
CD8 expression • CD73 overexpression • CD73 expression • NT5E overexpression
1year
Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer. (PubMed, Sci Rep)
Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8)
|
PD-L1 expression • CD73 expression
1year
A three-dimensional microenvironment alters CD73 expression in cervical cancer. (PubMed, Cell Biochem Funct)
Supporting the in vitro results, in silico analysis showed that three-dimensional spheres derived from cervical, thyroid and breast cancer presented decreased expression of CD73, when compared to their adherent counterparts. The decreased expression of CD73 in sphere-derived cells or CSC-enriched population reinforce its important role in cell adhesion, tumour spreading ability and metastasis, suggesting CD73 as potential target to be further investigated in cervical cancer.
Journal
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 expression
1year
Circular RNA circ_ASAP2 regulates drug sensitivity and functional behaviors of cisplatin-resistant gastric cancer cells by the miR-330-3p/NT5E axis. (PubMed, Anticancer Drugs)
Furthermore, circ_ASAP2 modulated cell DDP sensitivity and functional behaviors by targeting miR-330-3p. Knockdown of circ_ASAP2 promoted DDP sensitivity and suppressed malignant behaviors of DDP-resistant gastric cancer cells through targeting the miR-330-3p/NT5E axis.
Journal
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 expression • NT5E overexpression
|
cisplatin
1year
Molecular monitoring of glioblastoma's immunogenicity using a combination of Raman spectroscopy and chemometrics. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc)
We found that ZEB1 and CD73 influence T-cell and monocyte phenotype and promote monocyte differentiation into a population of mixed pro- and anti-tumorigenic macrophages (MΦs) and dendritic cells (DCs) respectively. In conclusion, Raman spectroscopy in combination with chemometrics enabled tracking T-cells and monocytes.
Journal
|
ZEB1 (Zinc Finger E-box Binding Homeobox 1)
|
CD73 expression
1year
[VIRTUAL] COMBINATORIAL INHIBITION OF TIGIT AND CD39 INCREASE T-CELL MEDIATED KILLING IN AML (EHA 2021)
Through inhibition of CD39 in combination with TIGIT T-cell mediated lysis could be increased in AML. These results provide a rationale to further evaluate the TIGIT checkpoint blockade in combination with inhibition of the purinergic signaling to improve T-cell mediated cytotoxicity in AML.
PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IL2RA (Interleukin 2 receptor, alpha) • IL7R (Interleukin 7 Receptor) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CCR7 (Chemokine (C-C motif) receptor 7) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
PD-1 expression • CD73 expression
1year
[VIRTUAL] How miRNAs affect the expression of immune checkpoint molecules (CIMT 2021)
Different from the NT5E inhibiting miRNAs above, we suspect indirect mechanisms for the miRNA-mediated enhancement of NT5E expression. In summary, microarray expression profiling was performed on miRNA transfected tumor cells to unravel the mechanisms responsible for the up-regulated NT5E expression observed.
PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
|
PD-1 expression • CD73 expression
1year
Increased Extracellular Adenosine in Radiotherapy-Resistant Breast Cancer Cells Enhances Tumor Progression through A2AR-Akt-β-Catenin Signaling. (PubMed, Cancers (Basel))
The upregulation of phospho-AKT, β-catenin, Snail, and vimentin expression in mice injected with RT-R-4T1 cells was also attenuated in mice injected with RT-R-4T1-A2AR-shRNA cells. These results suggest that A2AR is significantly upregulated in BC tissues, especially TNBC tissues, and ADO-mediated A2AR activation is involved in RT-R-TNBC invasion and metastasis through the AKT-β-catenin pathway.
Journal
|
VIM (Vimentin)
|
CD73 expression • VIM expression
1year
[VIRTUAL] Tumor-Responsive, Multifunctional CAR-NK Cells Cooperate with Impaired Autophagy to Infiltrate and Target Glioblastoma (ASGCT 2021)
To address insufficient homing of NK cells into the tumor bed, we combined these cells with chloroquine (CQ) as an adjuvant to inhibit autophagy in GBM and evaluated these cells against patient-derived intracranial GBM models in vivo (Fig.1D)... We built a novel, sophisticated combinatorial platform for GBM: a multifunctional immunotherapy based on genetically-engineered, human NK cells bearing multiple anti-tumor functions, including local tumor responsiveness, that addresses, for the first time, key drivers of GBM resistance to therapy: antigen escape, immunometabolic reprogramming of immune responses, and poor immune cell homing.
IO biomarker
|
CXCL10 (Chemokine (C-X-C motif) ligand 10) • NT5E (5'-Nucleotidase Ecto) • NKG2D (killer cell lectin like receptor K1)
|
CD73 expression
|
chloroquine phosphate
1year
[VIRTUAL] Preliminary safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of uliledlimab (TJ004309), a differentiated CD73 antibody, in combination with atezolizumab in patients with advanced cancer. (ASCO 2021)
One patient failed nivolumab and the other received no prior PD-(L)1 inhibitor treatment . Uliledlimab is safe and well tolerated up to 20 mg/kg Q3W and 15 mg/kg QW . Full saturation of circulating and cell-bound CD73 was achieved at doses ≥ 10 mg/kg . Uliledlimab exhibited evidence of clinical activity in both PD-(L)1 treatment naïve and refractory cancer patients with high archival tumor expression of CD73 .
Clinical • PK/PD data • Combination therapy • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD19 (CD19 Molecule) • NT5E (5'-Nucleotidase Ecto)
|
PD-L1 expression • CD73 expression
|
Opdivo (nivolumab) • Tecentriq (atezolizumab) • uliledlimab (TJD5)
1year
[VIRTUAL] Safety and efficacy of the anti-CD73 monoclonal antibody (mAb) oleclumab ± durvalumab in patients (pts) with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or EGFR-mutant non-small cell lung cancer (EGFRm NSCLC). (ASCO 2021)
Oleclumab ± durvalumab had a tolerable safety profile and combination therapy showed promising antitumor activity in EGFRm NSCLC . ORs and SD were durable, even in tumor types that are generally immunotherapy-resistant.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • GZMB (Granzyme B) • NT5E (5'-Nucleotidase Ecto)
|
EGFR mutation • CD73 expression
|
Imfinzi (durvalumab) • oleclumab (MEDI9447)
1year
CD73 Is Regulated by the EGFR-ERK Signaling Pathway in Non-small Cell Lung Cancer. (PubMed, Anticancer Res)
The results of this study may provide novel therapeutic strategies for the treatment of oncogene-driven NSCLC.
Journal • IO biomarker
|
NT5E (5'-Nucleotidase Ecto)
|
EGFR mutation • EGFR overexpression • CD73 expression
1year
Overexpression of CD73 in pancreatic ductal adenocarcinoma is associated with immunosuppressive tumor microenvironment and poor survival. (PubMed, Pancreatology)
CD73 overexpression is associated with poor differentiation, tumor size, and shorter survival, and is an independent prognostic factor in PDAC patients. CD73 overexpression is associated with decreased CD4, CD8 and CD21 TILs. Our data support that CD73 plays an important role in immunosuppressive tumor microenvironment and promote tumor progression in PDAC.
Journal
|
CD8 (cluster of differentiation 8) • NT5E (5'-Nucleotidase Ecto)
|
CD73 overexpression • CD73 expression • NT5E overexpression
1year
Immune-Inhibitory Gene Expression is Positively Correlated with Overall Immune Activity and Predicts Increased Survival Probability of Cervical and Head and Neck Cancer Patients. (PubMed, Front Mol Biosci)
However, high expression of seven immune suppression genes, including TWEAK-R, CD73, IL1 family and TGFb family genes, was significantly associated with decreased survival probability. Both scores also significantly associated with survival probability in HNSCC, and correlated with the previously established "Immunophenoscore." CESC and HNSCC tumors expressing genes predictive of T cell infiltrates (hot tumors) have a better prognosis, despite simultaneous expression of many immune inhibitory genes, than tumors lacking expression of genes associated with T cell infiltrates (cold tumors) whether or not these tumor express immune inhibitory genes.
Clinical • Journal • IO biomarker
|
CD73 expression
1year
Expression and Clinical Significance of CD73 in Acute Myeloid Leukemia Patients with NPM1 Mutation (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
The expression of CD73 was increased in AML patients with NPM1 gene mutation, and CD73 showed different prognostic significance in AML patients with different NPM1 gene mutation. The combination of clinicopathologic features, CD73 expression and NPM1 gene in AML patients is helpful to determine their prognosis and guide the formulation of relevant treatment plans.
Clinical • Journal
|
NPM1 (Nucleophosmin 1) • NT5E (5'-Nucleotidase Ecto)
|
NPM1 mutation • CD73 expression
over1year
High-dimensional analysis of the adenosine pathway in high-grade serous ovarian cancer. (PubMed, J Immunother Cancer)
Our study revealed the clinical, immunological, subtype-specific impacts of eADO signaling in HGSC, unveiled the chemoprotective effect of CD39 and supports the evaluation of eADO-targeting agents in patients with ovarian cancer.
Journal
|
CD8 (cluster of differentiation 8) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression
over1year
Influence of NSAIDs and methotrexate on CD73 expression and glioma cell growth. (PubMed, Purinergic Signal)
The aim of this study was to evaluate the effect of the NSAIDs, naproxen, piroxicam, meloxicam, ibuprofen, sodium diclofenac, acetylsalicylic acid, nimesulide, and ketoprofen on CD73 expression in GBM and mononuclear cells...For analysis of the mechanism of action of MTX, GBM cells were treated with APCP (CD73 inhibitor), dipyridamole (inhibitor of adenosine uptake), ABT-702 (adenosine kinase enzyme inhibitor), or caffeine (P1 adenosine receptor antagonist), before treatment with MTX and AMP, in the presence or not of mononuclear cells. In summary, only MTX increased the expression of CD73 in GBM cells decreasing cells viability by mechanisms independent of the adenosinergic system. Further studies are needed to understand the role of MTX in the GBM microenvironment.
Journal
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 overexpression • CD73 expression • NT5E overexpression
|
methotrexate • aspirin • dipyridamole • ibuprofen • meloxicam • naproxen • nimesulide • piroxicam
over1year
CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer. (PubMed, Sci Rep)
CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial-mesenchymal transition.
Journal
|
CDH1 (Cadherin 1) • VIM (Vimentin) • NT5E (5'-Nucleotidase Ecto)
|
CDH1 expression • CD73 expression • VIM expression
over1year
Identification of an Immune-Related Signature for Predicting Prognosis in Patients With Pancreatic Ductal Adenocarcinoma. (PubMed, Front Oncol)
In addition, PAIS was positively correlated with the infiltration of M2 macrophages in PDAC. This study highlighted the relationship between the immune response and prognosis in PDAC and developed a clinically feasible signature that might serve as a powerful prognostic tool and help further optimize the cancer therapy paradigm.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD276 (CD276 Molecule) • IDO1 (Indoleamine 2,3-dioxygenase 1) • IL20RB (Interleukin 20 Receptor Subunit Beta)
|
CD73 expression
over1year
[VIRTUAL] Activation of B cells by CD73 blocking antibodies (AACR 2021)
Our research has identified that oleclumab activates human peripheral blood B cells. Given the renewed interest in B-cell biology in IO, this is an area we believe warrants further clinical investigation.
IO biomarker
|
IL6 (Interleukin 6) • CD69 (CD69 Molecule) • NT5E (5'-Nucleotidase Ecto) • CD86 (CD86 Molecule)
|
CD73 expression
|
oleclumab (MEDI9447)
over1year
[VIRTUAL] Human CD73 knock-in mice facilitate evaluation of in vivo efficacy of anti-human CD73 cancer immunotherapies (AACR 2021)
Furthermore, in PD-1/PD-L1/CD73 triple KI humanized mice implanted with MC38 tumors, combined CD73 and PD-1/PD-L1 blockade showed greater tumor inhibition than monotherapies. Taken together, CD73 humanized mice and their variants are useful tools for in vivo efficacy evaluation of candidate human CD73 antibodies and combination therapies being considered for clinical trials.
Preclinical
|
NT5E (5'-Nucleotidase Ecto)
|
CD73 overexpression • CD73 expression • NT5E overexpression
over1year
[VIRTUAL] Phenogenomic characterization of immunomodulatory purinergic signaling in glioblastoma (AACR 2021)
Phenogenomic analysis of purinergic signaling in glioblastoma revealed correlations between CD73 expression and genotype, adenosine concentration, and clinical outcome. Spatial analysis revealed interaction between macrophages CD39 expression and tumor cell CD73 expression, suggesting that these populations may interact to suppress anti-tumor immunity. Anti-CD73 therapy may provide therapeutic benefits in glioblastoma by blunting immunosuppressive and oncogenic adenosine signaling.
PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
|
PD-L1 expression • EGFR amplification • EGFR expression • TP53 expression • CD73 expression
over1year
[VIRTUAL] Blocking adenosine production with ORIC-533, a CD73 inhibitor with best-in-class properties, reverses immunosuppression in high-AMP environments (AACR 2021)
Taken together, these preclinical results indicate the CD73 inhibitor ORIC-533 has best-in-class properties in reversing immunosuppression in tumors. ORIC-533 is currently undergoing GLP studies to support an IND filing in the first half of 2021.
Late-breaking abstract
|
CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • NT5E (5'-Nucleotidase Ecto)
|
CD73 overexpression • IL2RA expression • CD73 expression • NT5E overexpression
|
ORIC-533
over1year
[VIRTUAL] Preclinical characterization of Sym024, a novel anti-CD73 antibody (AACR 2021)
In vitro one-way mixed lymphocyte reaction results demonstrate the utility of combining CD73 inhibition with PD-1 blockade, as Sym024 acts to reverse the immune suppressive effect of adenosine production, thereby allowing effective T cell activation by an anti-PD-1 antibody (Sym021). Dose-proportional and linear pharmacokinetics (PK) was observed at high dose levels while nonlinear PK became evident at lower exposure levels. Sym024 is currently under clinical investigation.
Preclinical • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • NT5E (5'-Nucleotidase Ecto)
|
CD73 overexpression • CD73 expression • NT5E overexpression
|
Sym021 • Sym024
over1year
[VIRTUAL] CD73 inhibitor oleclumab plus osimertinib for advanced EGFRm NSCLC: First report of a Phase 1b/2 study (AACR 2021)
Oleclumab + osi was well tolerated at RP2D. Compared to T790M-negative EGFRm NSCLC pts in a prior study of osi monotherapy, ORR was similar (21% vs 19%) but mPFS was longer (2.8 vs 11.0 mos). Table 1.
P1/2 data
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR negative • CD73 overexpression • CD73 expression • EGFR T790M negative
|
Tagrisso (osimertinib) • oleclumab (MEDI9447)
over1year
CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity. (PubMed, Front Cell Dev Biol)
In agreement, when adoptively transferred, antigen-specific CD73-deficient CD8+ T cells were more effective in reducing the tumor burden in B16.OVA melanoma-bearing mice and presented lower levels of exhaustion markers than wild type cells. All these data suggest an autocrine effect of CD73-mediated adenosine production, limiting differentiation and cytotoxic T cells' metabolic fitness.
Journal
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • GZMB (Granzyme B) • ADORA2A (Adenosine A2a Receptor) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD8 expression • CD73 expression
over1year
Loss of CD73 shifts transforming growth factor-β1 (TGF-β1) from tumor suppressor to promoter in endometrial cancer. (PubMed, Cancer Lett)
Further loss of CD73 in CD73 expressing advanced stage EC cells increased TGF-β-mediated stress fibers, signaling, and invasiveness, whereby adenosine A1 receptor agonist, CPA, dampened TGF-β-mediated invasion. These data identify CD73 loss as essential for shifting TGF-β activity in EC.
Journal
|
CCND1 (Cyclin D1) • TGFB1 (Transforming Growth Factor Beta 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
CCND1 expression • CD73 expression
over1year
An Investigational Immuno-therapy Study of Experimental Medication BMS-986179 Given Alone and in Combination With Nivolumab (clinicaltrials.gov)
P1/2, N=268, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting | Trial completion date: Sep 2022 --> Feb 2023 | Trial primary completion date: Nov 2020 --> Feb 2023
Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
|
CD73 expression
|
Opdivo (nivolumab) • BMS-986179
over1year
Targeting the purinergic pathway in breast cancer and its therapeutic applications. (PubMed, Purinergic Signal)
Several purinergic pathways have been found to be involved in BC cell survival and progression. In this review, in addition to analyzing the pathways involved, we reviewed the therapeutic interventions already studied for BC related to the purinergic system, as well as to other possible therapeutic targets.
Review • Journal
|
ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression
over1year
Immune profiling and immunotherapeutic targets in pancreatic cancer. (PubMed, Ann Transl Med)
Multiple genes including TIM3, VISTA, CCL2, CCR2, TGFB1, CD73, and CD39 had significantly higher mean expression versus the comparison cohort, while three genes (LAG3, GITR, CD38) had significantly lower mean expression. This study demonstrates that a clinically relevant unique profile of immune markers can be identified in PDAC and be used as a roadmap for personalized immunotherapeutic decision-making strategies.
Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • CD38 (CD38 Molecule) • LAG3 (Lymphocyte Activating 3) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TGFB1 (Transforming Growth Factor Beta 1) • CCL2 (Chemokine (C-C motif) ligand 2) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
PD-L1 expression • PD-L1 negative • CD73 expression
over1year
Molecular dynamics of targeting CD38 in multiple myeloma. (PubMed, Br J Haematol)
Further, they are internalised in FcR cells with significant functional modifications. These observations have relevance for improving anti-CD38 therapeutic antibodies through targeting this mechanism and its sequelae.
Journal • PD(L)-1 Biomarker • IO biomarker
|
ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
PD-L1 expression • CD73 expression
over1year
SYNERGY: Paclitaxel + Carboplatin + Durvalumab With or Without Oleclumab for Previously Untreated Locally Recurrent Inoperable or Metastatic TNBC (clinicaltrials.gov)
P1/2, N=171, Recruiting, Jules Bordet Institute | Trial completion date: May 2023 --> Oct 2023 | Trial primary completion date: Feb 2023 --> Jul 2023
Trial completion date • Trial primary completion date • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • NT5E (5'-Nucleotidase Ecto)
|
PD-L1 expression • HER-2 positive • HR positive • HER-2 negative • ER negative • CD73 expression
|
carboplatin • Imfinzi (durvalumab) • paclitaxel • oleclumab (MEDI9447)
over1year
Detection of CD39 and a Highly Glycosylated Isoform of Soluble CD73 in the Plasma of Patients with Cervical Cancer: Correlation with Disease Progression. (PubMed, Mediators Inflamm)
In addition, the levels of transforming grow factor-β (TGF-β) in the PFPs of patients with LSIL, HSIL and CC positively correlated with those of CD39 (r = 0.4432, p < 0.001) and CD73 (r = 0.5786, p < 0.001). These results suggest that persistent infection by HR-HPV and the concomitant production of TGF-β promote the expression of CD39 and CD73 to favor CC progression through Ado generation.
Clinical • Journal
|
ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression
over1year
Enhanced expression of CD39 and CD73 on T cells in the regulation of anti-tumor immune responses. (PubMed, Oncoimmunology)
Our findings suggest that the upregulation of ectonucleotidase expression in T cells promotes extracellular adenosine accumulation and represents an important mechanism of homeostatic immune auto-regulation, which could be hijacked by tumors to evade anti-cancer immunity. Targeting CD39 and CD73 can open new avenues for cancer immunotherapy.
Journal • PD(L)-1 Biomarker • IO biomarker
|
IFNG (Interferon, gamma) • PD-1 (Programmed cell death 1) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
PD-1 expression • CD73 expression
over1year
Upregulation of CD73 Confers Acquired Radioresistance and is Required for Maintaining Irradiation-selected Pancreatic Cancer Cells in a Mesenchymal State. (PubMed, Mol Cell Proteomics)
Our findings suggest that expression alterations in the IR-selected pancreatic cancer cells result in hyperactivation of the growth factor/cytokine signaling that promotes epithelial-mesenchymal plasticity and enhancement of DNA repair. Our results also suggest that CD73, potentially a novel downstream factor of the enhanced growth factor/cytokine signaling, confers acquired radioresistance by inactivating proapoptotic protein BAD via phosphorylation of BAD at Ser-136 and by maintaining the radioresistant pancreatic cancer cells in a mesenchymal state.
Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3)
|
CD73 overexpression • CD73 expression
over1year
Identification of neuroblastoma cell lines with uncommon TAZ/mesenchymal stromal cell phenotype with strong suppressive activity on natural killer cells. (PubMed, J Immunother Cancer)
We identified a novel NB immunoregulatory subset that: (i) displayed phenotypic and functional properties of MSC, (ii) mediated multifactorial resistance to NK-cell-induced killing and (iii) efficiently inhibited, in coculture, the cytotoxic activity of NK cells against target cells through a TAZ-dependent mechanism. These findings indicate that targeting novel cellular and molecular components may disrupt the immunomodulatory milieu of the NB microenvironment ameliorating the response to conventional treatments as well as to advanced immunotherapeutic approaches, including adoptive transfer of NK cells and chimeric antigen receptor T or NK cells.
Preclinical • Journal • IO biomarker
|
MCAM
|
CD73 expression
over1year
Generation of a new immortalized human lung pericyte cell line: a promising tool for human lung pericyte studies. (PubMed, Lab Invest)
We further demonstrated that Fli-1 regulates inflammatory responses in immortalized human lung pericytes. To summarize, we successfully established an immortalized human lung pericyte cell line, which serves as a promising tool for in vitro pericyte studies to understand human lung pericyte physiology and pathophysiology.
Preclinical • Journal
|
PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CD44 • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • MCAM
|
CD73 expression
over1year
Ectonucleotidase CD39 is highly expressed on ATLL cells and is responsible for their immunosuppressive function. (PubMed, Leukemia)
Overall, we found that ATLL cells express CD39 at a high rate, and our results suggest that this helps ATLL cells escape antitumor immunity through the extracellular ATPDase-Adenosine cascade. These findings will guide future clinical strategies for ATLL treatment.
Journal
|
CD8 (cluster of differentiation 8) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression
over1year
Mesenchymal stromal cells in adipose tissue of breast cancer patients: a cross-sectional study. (PubMed, Cell Mol Biol (Noisy-le-grand))
Our result indicated that Mesenchymal stromal cells are seen more in the tumor microenvironment of younger breast cancer patients. Also, patients having mesenchymal stromal cells may have milder disease and lower disease stage.
Clinical • Observational data • Journal
|
CD14 • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ITGAM (Integrin, alpha M)
|
CD73 expression
over1year
CD73, Tumor Plasticity and Immune Evasion in Solid Cancers. (PubMed, Cancers (Basel))
We also discuss data that support a link between CD73 expression and tumor plasticity, contributing to dissemination as well as treatment resistance. Collectively, targeting CD73 may represent a novel treatment approach for solid cancers.
Review • Journal • IO biomarker
|
CD73 expression
over1year
CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma. (PubMed, Cancer Immunol Immunother)
Our study suggests that higher CD73 expression is associated with an overall augmented host immune response, suggesting potential implications in the immune pathobiology of early stage lung adenocarcinoma. Our findings warrant further studies to explore the role of CD73 in immunotherapeutic response of LUAD.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression • CD73 expression
over1year
Increased expression of adenosine 2A receptors in metastatic renal cell carcinoma is associated with poorer response to anti-vascular endothelial growth factor agents and anti-PD-1/Anti-CTLA4 antibodies and shorter survival. (PubMed, Cancer Immunol Immunother)
Our findings suggest that the expression of A2AR and PD-L1 in the primary tumors in RCC might predict the outcomes of treatment with anti-VEGF agents and ICIs and that the A2AR pathway might be a molecular target for immunotherapy.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
PD-L1 expression • CD73 expression
over1year
Characterization of the immune landscape of EGFR-mutant NSCLC identifies CD73/adenosine pathway as a potential therapeutic target. (PubMed, J Thorac Oncol)
Our work demonstrated that EGFR-mutant NSLCLC has an immune-inert phenotype. We identified the CD73/adenosine pathway as a potential therapeutic target for EGFR-mutant NSCLC.
Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
|
EGFR mutation • TMB-L • CD73 expression
over1year
Serum CD73 is a prognostic factor in patients with metastatic melanoma and is associated with response to anti-PD-1 therapy. (PubMed, J Immunother Cancer)
Our data indicate the relevance of serum CD73 in patients with advanced melanoma receiving anti-PD-1 therapy and support further investigation on targeting CD73 in combination with anti-PD-1 antibodies.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
|
CD73 expression
|
Keytruda (pembrolizumab) • Opdivo (nivolumab)
over1year
Direct and Indirect Regulators of Epithelial-Mesenchymal Transition (EMT)-mediated Immunosuppression in Breast Carcinomas. (PubMed, Cancer Discov)
Most strikingly, mixed tumors in which minority populations of carcinoma cells no longer express CD73, are now sensitized to anti-CTLA4 ICB. Finally, loss of CD73 also enhances the efficacy of anti-CTLA4 ICB during the process of metastatic colonization.
Journal
|
SPP1 (Secreted Phosphoprotein 1) • CSF1 (Colony stimulating factor 1)
|
CD73 expression
over1year
Single-Cell Sequencing of Glioblastoma Reveals Central Nervous System Susceptibility to SARS-CoV-2. (PubMed, Front Oncol)
Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs, and NPCs, from clinical specimens. These findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2-infected patients with neural symptoms, especially those who suffered a glioma.
Journal
|
CD31 (Platelet and endothelial cell adhesion molecule 1)
|
CD31 expression • CD73 expression
over1year
Highly expressed tumoral emmprin and stromal CD73 predict a poor prognosis for external auditory canal carcinoma. (PubMed, Cancer Sci)
The colocalization of emmprin and CD73 was enhanced in not only the peripheral cells of the tumor cell clusters that interact with fibroblasts but also in the cells of intra-tumor clusters. Overall, this study provides novel insights into the roles of emmprin, CD73, and MMP-2 in tumor invasiveness.
Journal
|
MMP2 (Matrix metallopeptidase 2)
|
CD73 expression
over1year
EpCAMCD73 mark epithelial progenitor cells in postnatal human lung and is associated with pathogenesis of pulmonary disease including lung adenocarcinoma. (PubMed, Am J Physiol Lung Cell Mol Physiol)
In conclusion, EpCAMCD73 cells are a rare novel epithelial progenitor cell in human lung. Importantly, re-emergence of CD73 in lung adenocarcinoma enriched in negative immune checkpoint molecules may serve as a novel therapeutic target.
Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1)
|
CD73 expression • EPCAM expression
over1year
Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines. (PubMed, Sci Rep)
Overall, compared to photon radiation, the effects of carbon ion radiation appeared to be enhanced at higher dose range for EO771 cells and extenuated at lower dose range for PDA30364/OVA cells. Our data show for the first time that equivalent doses of carbon ion and photon irradiation exert similar immunomodulating effects on the cell lines of both tumor entities, highlighted by an enhanced susceptibility to CTL mediated cytolysis in vitro.
Preclinical • Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1)
|
CD73 expression
over1year
[VIRTUAL] The immune checkpoint CD73 (NT5E) in gastric adenocarcinoma (GAC): Biological characterization and clinical implications. (ASCO-GI 2021)
In this hypothesis-generating analysis, we provided insights into CD73 expression pattern, co-expression networking and prognostic significance in GAC. Future studies in clinically annotated populations are warranted to confirm the value of CD73 in GAC.
Clinical
|
CAV1 (Caveolin 1)
|
CD73 expression
over1year
Radiation-induced alterations in immunogenicity of a murine pancreatic ductal adenocarcinoma cell line. (PubMed, Sci Rep)
For the PDA cell line investigated, our data show for the first time that single photon doses ≥ 5 Gy effectively inhibit colony formation and induce a G2/M cell cycle arrest. Furthermore, expression levels of immunomodulatory cell surface molecules became altered possibly enhancing the susceptibility of tumour cells to CTL lysis.
Preclinical • Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
|
CD73 expression
over1year
The expression of CD73 on pathological B-cells is associated with shorter overall survival of patients with CLL. (PubMed, Neoplasma)
Clinically, patients with higher levels of CD73 versus those with lower expression presented with shorter overall survival (median OS of 65 vs. 113 months, p < 0.05). Our data indicate that CD73 may play a role in CLL pathophysiology, is correlated with poor clinical and biological prognostic factors and may be of potential value as a prognostic marker and therapeutic target.
Clinical • Journal
|
B2M (Beta-2-microglobulin)
|
CD73 expression
over1year
Enzymatic Activity of CD73 Modulates Invasion of Gliomas via Epithelial-Mesenchymal Transition-Like Reprogramming. (PubMed, Pharmaceuticals (Basel))
Furthermore, application of phosphodiesterase inhibitor pentoxifylline, a potent immunomodulator, effectively inhibited ZEB1 and CD73 expression and significantly decreased viability, clonogenicity, and invasion of GSC in vitro cultures...Taken together, our data indicate that CD73 is an exciting novel target in GBM therapy. Moreover, pharmacological interference, resulting in disturbed ADO signalling, provides new opportunities to innovate GBM therapy.
Journal
|
ZEB1 (Zinc Finger E-box Binding Homeobox 1)
|
CD73 expression • ZEB1 expression
|
pentoxifylline
over1year
Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma. (PubMed, J Immunother Cancer)
High CD73 expression portends significantly worse survival outcomes independent of stage and grade. Our findings provide compelling support for targeting the immunosuppressive and proangiogenic CD73-adenosine pathway in RCC.
Journal
|
PD-1 expression • CD73 expression
over1year
MiRNA-340-5p mediates the functional and infiltrative promotion of tumor-infiltrating CD8 T lymphocytes in human diffuse large B cell lymphoma. (PubMed, J Exp Clin Cancer Res)
MiR-340-5p promoted CD8 T-TIL infiltration and antitumor function by regulating KMT5A and COP1 and further activating CD73 ubiquitination. MiR-340-5p is potentially a novel target for DLBCL immunotherapy.
Journal
|
CD8 (cluster of differentiation 8) • MIR340 (MicroRNA 340)
|
CD73 overexpression • CD73 expression
over1year
CD73 blockade promotes dendritic cell infiltration of irradiated tumors and tumor rejection. (PubMed, Cancer Immunol Res)
In the absence of radiotherapy-induced IFN-I, blockade of CD73 was required for rejection of the irradiated tumor and for systemic tumor control (abscopal effect) in the context of CTLA-4-blockade. These results suggest that CD73 may be a radiation-induced checkpoint, and that CD73 blockade in combination with radiotherapy and immune checkpoint blockade might improve patient response to therapy.
Journal
|
CD8 (cluster of differentiation 8) • CD38 (CD38 Molecule) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
|
CD73 expression
over1year
Identification of a regulatory Vδ1 gamma delta T cell subpopulation expressing CD73 in human breast cancer. (PubMed, J Leukoc Biol)
We then found that in human breast tumors, γδ T cells were present particularly in late stage breast cancer samples, and that ∼20% of tumor-infiltrating γδ T cells expressed CD73. Taken together, these results suggest that regulatory γδ T cells are present in the breast cancer microenvironment and may display immunosuppressive functions through the production of immunosuppressive molecules, such as IL-10, IL-8, and adenosine, thus promoting tumor growth.
Clinical • Journal
|
CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL10 (Interleukin 10)
|
CD73 expression
over1year
[VIRTUAL] High-Dimensional and Single-Cell Transcriptome Analysis of AITL Tumor Microenvironment Reveals Gross Expansion of Novel Dysfunctional CD8+ T Cell Populations, Global Shift in B Cell Phenotypes (ASH 2020)
High-dimensional and single-cell transcriptome analysis of the AITL microenvironment yielded several novel insights which have not been previously described in this malignancy. Highlights include the gross expansion of distinct CD8+ populations – the majority of which are of an exhausted, dysfunctional phenotype featuring marked upregulation of XCL2 and XCL1 – and the global loss of CXCR5 and CD73 expression among AITL CD19+ B cell populations. Taken together, this suggests the presence of aberrant non-malignant immune subsets within the AITL microenvironment which may contribute to novel mechanisms of immune escape.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • CD19 (CD19 Molecule) • IFNG (Interferon, gamma) • PD-1 (Programmed cell death 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CCR7 (Chemokine (C-C motif) receptor 7) • ICOS (Inducible T Cell Costimulator)
|
CD19 expression • CD73 expression
over1year
[VIRTUAL] Increased Frequency of TOX+ CD39+ TIGIT+ CD73- CD8+ T Cells in Patients with Newly Diagnosed AML (ASH 2020)
In contrast downregulation of CD127 and TCF-1 was found in these cells. These data might contribute to CD8+ T cell exhaustion in AML and support further functional analysis to investigate the relevance of combinatorial inhibition of TIGIT and CD39.
Clinical • IO biomarker
|
CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • IL7R (Interleukin 7 Receptor) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
|
CD73 expression
over1year
CXCR4 Inhibition Counteracts Immunosuppressive Properties of Metastatic NSCLC Stem Cells. (PubMed, Front Immunol)
Treatment of spheroids with anti-CXCR4 rescued T cell cytotoxic activity and prevented TAM polarization, likely by causing the decrease of adenosine and IL-10 production. Overall, we provide evidence that the subset of lung MICs shows high potential to escape immune control and that inhibition of CXCR4 can impair both MICs dissemination and their immunosuppressive activity, therefore potentially providing a novel therapeutic target in combination therapies to improve efficacy of NSCLC treatment.
Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • CD38 (CD38 Molecule) • CD133 • IL10 (Interleukin 10)
|
CD73 expression
over1year
A Monte Carlo framework for managing biological variability in manufacture of autologous cell therapy from mesenchymal stromal cells therapies. (PubMed, Cytotherapy)
Finally, four engineering runs of the candidate process were conducted and a range of relevant quality parameters measured including expression of markers CD105, CD73, CD44, CD45, CD34, CD11b, CD19, HLA-DR, CD146 (melanoma cell adhesion molecule), CD106 (vascular cell adhesion molecule) and SSEA-4, specific metabolic activity and vascular endothelial growth factor secretion, and osteogenic differentiation potential. Our approach of using estimated distributions from publicly available information provides a route for data-poor earl- stage developers to plan manufacture with defined risk based on rational assumptions; furthermore, the models produced by such assumptions can be used to evaluate candidate processes, and can be incrementally improved with accumulating distribution understanding or subdivision by new process variables.
Journal
|
CD19 (CD19 Molecule) • CD44 • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ITGAM (Integrin, alpha M) • MCAM • VCAM1 (Vascular Cell Adhesion Molecule 1)
|
CD44 expression • CD73 expression
over1year
CD73 Overexpression Promotes Progression and Recurrence of Papillary Thyroid Carcinoma. (PubMed, Cancers (Basel))
Taken together, CD73 expression promotes tumor progression and predicts low recurrence-free survival. Targeting the CD73-adenosine axis in the tumor microenvironment offers an attractive pathway for therapeutic strategies aimed at advanced PTC.
Journal
|
BRAF (B-raf proto-oncogene)
|
BRAF mutation • CD73 overexpression • CD73 expression
over1year
Human Umbilical Cord Wharton's Jelly-derived Mesenchymal Stem Cells Labeled with Mn2+ and Gd3+ Co-doped CuInS2-ZnS Nanocrystals for Multi-modality Imaging in Tumor Mice Model. (PubMed, ACS Appl Mater Interfaces)
Interestingly, CIS-ZMGS-NCs labeled WJ-MSCs exhibit near-infrared fluorescence (NIR) with quantum yield (QY) of 84%, radiant intensity ~3.999 x 1011 (p/sec/cm2/sr)/(µW/cm2), magnetic relaxivity (longitudinal r1=2.26 mM-1s-1, transverse r2=16.47 mM-1s-1) and X-ray attenuation (78 HU) potential for early non-invasive multi-modality imaging of a subcutaneous-melanoma in B16F10-tumor-bearing C57BL/6-mice in 6 h. The ex vivo imaging and inductively-coupled plasma mass-spectroscopy (ICP-MS) analyses of excised organs along with confocal-microscopy and immuno-fluorescence of tumor results also significantly confirmed positive-tropism of CIS-ZMGS-NCs labeled WJ-MSCs in the tumor-environment. Hence, we propose the magneto-fluorescent CIS-ZMGS-NCs labeled WJ-MSCs as a next-generation nano-bioprobe of three commonly used imaging-modalities for stem cells-assisted anti-cancer therapy and tracking tissue/organ regenerations.
Preclinical • Journal
|
CD44 • VIM (Vimentin)
|
CD73 expression • VIM expression
over1year
Ectonucleotidase CD73 and CD39 expression in non-small cell lung cancer relates to hypoxia and immunosuppressive pathways. (PubMed, Life Sci)
Ectonucleotidases are up-regulated in cancer cells, CAFs, and TILs in lung tumors. Such overexpression is linked with regulatory TIL-phenotype and PD-L1 up-regulation by cancer cells. Overexpression of LDH5 is up-regulated by adenosine, creating a vicious cycle, as the high amounts of ATP produced by LDH5-mediated anaerobic glycolysis promote the production of adenosine by a tumor microenvironment rich in ectonucleotidases.
Journal • PD(L)-1 Biomarker
|
LDHA (Lactate dehydrogenase A) • PD-1 (Programmed cell death 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • FOXP3 (Forkhead Box P3)
|
PD-L1 expression • CD73 expression • HIF1A expression • FOXP3 expression • TILs
over1year
[VIRTUAL] Natural killer cells engineered with an inducible, responsive genetic construct targeting TIGIT and CD73 to relieve immunosuppression within the GBM microenvironment (SITC 2020)
Further, engineered NK cells (T-PNK) expressed significantly higher levels of CD107a in response to GBM43 stimulation than non-engineered PNK at E:T ratios 2.5:1 and 10:1 (figure 3).Download figure Open in new tab Download powerpoint Abstract 123 Figure 1 TIGIT-synNotch gene expressionGene expression (left: %, right, MFI) of electroporated NK cells engineered with anti-CD73 and TIGIT blocking mRNADownload figure Open in new tab Download powerpoint Abstract 123 Figure 2 Engineered NK cell cytotoxicityCytotoxicity of NK cells against GBM43 cells at E:T ratios of 2.5:1, 5:1, and 10:1. NK cells were either un-transfected (with and without CD73 and TIGIT mAbs), transfected with the TIGIT-synNotch construct, or transfected with the TIGIT-synNotch and CD73 genetic constructsDownload figure Open in new tab Download powerpoint Abstract 123 Figure 3 Engineered NK cell degranulationCD107a expression measured on transfected and non-transfected NK cells stimulated with GBM43 at E:T ratios of 2.5:1, 5:1, and 10:1 Conclusions Overall, we have shown that co-targeting CD155 and CD73 in a localized, responsive manner can dampen immunosuppression and significantly enhance the killing potential of engineered NK cells against aggressive patient-derived GBM tumors.
IO biomarker
|
CD73 overexpression • CD73 expression
over1year
[VIRTUAL] Natural killer cells engineered with an inducible, responsive genetic construct targeting TIGIT and CD73 to relieve immunosuppression within the GBM microenvironment (SITC 2020)
Further, engineered NK cells (T-PNK) expressed significantly higher levels of CD107a in response to GBM43 stimulation than non-engineered PNK at E:T ratios 2.5:1 and 10:1 (figure 3).Download figure Open in new tab Download powerpoint Abstract 123 Figure 1 TIGIT-synNotch gene expressionGene expression (left: %, right, MFI) of electroporated NK cells engineered with anti-CD73 and TIGIT blocking mRNADownload figure Open in new tab Download powerpoint Abstract 123 Figure 2 Engineered NK cell cytotoxicityCytotoxicity of NK cells against GBM43 cells at E:T ratios of 2.5:1, 5:1, and 10:1. NK cells were either un-transfected (with and without CD73 and TIGIT mAbs), transfected with the TIGIT-synNotch construct, or transfected with the TIGIT-synNotch and CD73 genetic constructsDownload figure Open in new tab Download powerpoint Abstract 123 Figure 3 Engineered NK cell degranulationCD107a expression measured on transfected and non-transfected NK cells stimulated with GBM43 at E:T ratios of 2.5:1, 5:1, and 10:1 Conclusions Overall, we have shown that co-targeting CD155 and CD73 in a localized, responsive manner can dampen immunosuppression and significantly enhance the killing potential of engineered NK cells against aggressive patient-derived GBM tumors.
IO biomarker
|
CD73 overexpression • CD73 expression
almost2years
Identification and Expression Analysis of CD73 Inhibitors in Cervical Cancer. (PubMed, Med Chem)
Among all synthesized compounds (3a-3i), Compound 3h (E)-N'-((6-ethyl-4-oxo-4H-chromen-3-yl) methylene)-4-methylbenzenesulfonohydrazide was identified as most potent compound. Additional expression studies conducted on HeLa cell line proved that this compound successfully decreased the expression level of CD73 and thus inhibiting the growth and proliferation of cancer cells.
Journal
|
CD73 expression
almost2years
Enhanced migration of breast and lung cancer cells deficient for cN-II and CD73 via COX-2/PGE2/AKT axis regulation. (PubMed, Cell Oncol (Dordr))
Our results highlight new cell-specific roles of cN-II and CD73 in cancer cell biology and provide insight into their interactions with different intracellular pathways.
Journal
|
MMP2 (Matrix metallopeptidase 2) • MMP9 (Matrix metallopeptidase 9)
|
CD73 expression
almost2years
Tissue Immune Profile: A Tool to Predict Response to Neoadjuvant Therapy in Triple Negative Breast Cancer. (PubMed, Cancers (Basel))
The combined immune profile is more accurate in predicting pCR (AIC 68.3; BIC 74.5) as compared to single biomarkers. The association between TIP+ and pCR can be proposed as a novel link between immune background and response to chemotherapy in TNBC, highlighting the need to consider an immunological patients' profile rather than single biomarkers.
Clinical • Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression • CD73 expression • TILs
almost2years
Dual mechanisms of novel CD73-targeted antibody and antibody-drug conjugate in inhibiting lung tumor growth and promoting antitumor immune-effector function. (PubMed, Mol Cancer Ther)
We developed two novel series of CD73 antibody Ab001/Ab002 and humanized version Hu001/Hu0002, which demonstrated high CD73 binding affinity, potent enzyme inhibition and efficiently protected effector T lymphocyte function from adenosine/cancer-imposed toxicity. Studies with human PBMC-derived systems confirmed CD73-ADC as fully functional in protecting effector T cells and stimulating DCs thus providing dual benefits in killing CD73-high tumors and improving cancer immunity response. These results warrant clinical investigation of CD73-targeted antibody and ADC for treating advanced lung cancer.
Journal
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
CD73 expression
|
FB3001 • ProCase (AB002)
almost2years
Expression of CD73 is associated with tumor progression and intratumoral inflammation in breast cancer. (PubMed, Asia Pac J Clin Oncol)
In conclusion, this study showed that CD73 expression is associated with tumor progression and inflammation in breast cancer. Our results suggest that CD73 has a potential as a prognostic marker and a therapeutic target of breast cancer.
Journal
|
PGR (Progesterone receptor)
|
CD73 expression
almost2years
[VIRTUAL] Evaluation of combined biomarkers for tumor response to immunotherapy (I / O) in patients with advanced non-small cell lung cancer (NSCLC) (DGHO 2020)
43/56 pts received nivolumab, 15 pembrolizumab in different therapy lines (from 1st to 5th). The combination of different biomarkers may better predict responses to I/O than PD-L1 alone and improve the selection of patients that benefit from I/O treatment.
Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
|
PD-L1 expression • STK11 mutation • PD-L1 negative • KEAP1 mutation • CD73 expression • TMB + PD-L1 expression
|
Keytruda (pembrolizumab) • Opdivo (nivolumab)
almost2years
[VIRTUAL] Evaluation of combined biomarkers for tumor response to immunotherapy (I / O) in patients with advanced non-small cell lung cancer (NSCLC) (DGHO 2020)
43/56 pts received nivolumab, 15 pembrolizumab in different therapy lines (from 1st to 5th). The combination of different biomarkers may better predict responses to I/O than PD-L1 alone and improve the selection of patients that benefit from I/O treatment.
Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
|
PD-L1 expression • STK11 mutation • PD-L1 negative • KEAP1 mutation • CD73 expression • TMB + PD-L1 expression
|
Keytruda (pembrolizumab) • Opdivo (nivolumab)
almost2years
[VIRTUAL] Evaluation of combined biomarkers for tumor response to immunotherapy (I / O) in patients with advanced non-small cell lung cancer (NSCLC) (DGHO 2020)
43/56 pts received nivolumab, 15 pembrolizumab in different therapy lines (from 1st to 5th). The combination of different biomarkers may better predict responses to I/O than PD-L1 alone and improve the selection of patients that benefit from I/O treatment.
Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
|
PD-L1 expression • STK11 mutation • PD-L1 negative • KEAP1 mutation • CD73 expression • TMB + PD-L1 expression
|
Keytruda (pembrolizumab) • Opdivo (nivolumab)
almost2years
Sustained activation of notch signaling maintains tumor-initiating cells in a murine model of liposarcoma. (PubMed, Cancer Lett)
Most importantly, CRISPR-mediated disruption of Notch abrogated the tumorigenic properties of mLPS1 cells. These results reveal a key role of Notch signaling in maintaining TICs in LPS.
Preclinical • Journal
|
CD133
|
CD73 expression
almost2years
Decreased Equilibrative Nucleoside Transporter 1 (ENT1) Activity Contributes to the High Extracellular Adenosine Levels in Mesenchymal Glioblastoma Stem-Like Cells. (PubMed, Cells)
We did not observe significant differences between the expression of proteins involved in the metabolization of adenosine among the GCSs subtypes. In conclusion, the lower expression and activity of the ENT1 transporter in mesenchymal GSCs contributes to the high level of extracellular adenosine that these GSCs present.
Journal
|
CD73 expression
almost2years
SYNERGY: Paclitaxel + Carboplatin + Durvalumab With or Without Oleclumab for Previously Untreated Locally Recurrent Inoperable or Metastatic TNBC (clinicaltrials.gov)
P1/2, N=171, Recruiting, Jules Bordet Institute | Trial completion date: Dec 2022 --> May 2023 | Trial primary completion date: Sep 2022 --> Feb 2023
Trial completion date • Trial primary completion date • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • NT5E (5'-Nucleotidase Ecto)
|
PD-L1 expression • HER-2 positive • HR positive • HER-2 negative • ER negative • CD73 expression
|
carboplatin • Imfinzi (durvalumab) • paclitaxel • oleclumab (MEDI9447)
almost2years
Cancer-associated fibroblasts enhance the chemoresistance of CD73 hepatocellular carcinoma cancer cells via HGF-Met-ERK1/2 pathway. (PubMed, Ann Transl Med)
Also, we found that CD73 promote sorafenib and cisplatin resistance in HCC, and CD73 HCC cells indicated the higher capability of tumorigenicity compared to CD73 HCC cells in vivo. Furthermore, HGF further enhanced the chemoresistant characteristics of CD73 tumor cells. Our findings collectively suggest that CD73 is a vital HCC-chemoresistance force controlled by cross-talking between CAFs and HCC cells, thereby establishing CD73 as a potential new therapeutic target for HCC.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • HGF (Hepatocyte growth factor)
|
CD73 expression
|
cisplatin • sorafenib
almost2years
Adenosine and adenosine receptors in colorectal cancer. (PubMed, Int Immunopharmacol)
These findings imply that components of this axis can be considered as a worthy target for colorectal cancer immunotherapy. In this review, we summarized the role of CD73/CD39/adenosine/ARs in the immunopathogenesis of colorectal cancer.
Review • Journal
|
CD73 expression
almost2years
1α, 25-Dihydroxyvitamin D3 alters ectonucleotidase expression and activity in human cutaneous melanoma cells. (PubMed, J Cell Biochem)
To the best of our knowledge, we showed for the first time a mechanism of control of adenosine production via modulation of the purinergic system in cutaneous melanoma cells treated with the active metabolite of vitamin D. This study provides original information regarding mechanisms, in which vitamin D plays a key role in preventing tumor progression in human melanoma cells.
Journal
|
CD73 expression
almost2years
Glioma patient profiling reveals the dominant immune suppressive adenosine axis is refractory to immune function restoration. (PubMed, JCI Insight)
This study illustrates vetting steps that should be considered prior to clinical trial implementation for immunotherapy resistant cancers including testing an agents ability to restore immunological function in the context of intended use.
Clinical • Journal • PD(L)-1 Biomarker
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • ITGAM (Integrin, alpha M)
|
IDH1 mutation • CD73 expression
almost2years
PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • CD28 (CD28 Molecule) • CD27
|
CD8 expression • CD73 expression
almost2years
Expression of VEGF, CD73 and their relationship with clinical pathology, microvessel density, and prognosis in renal cell carcinoma. (PubMed, Transl Androl Urol)
The five-year mortality rate of patients with positive expressions of VEGF and CD73 was higher than that of patients with negative expressions (P<0.05). The expressions of VEGF and CD73 in RCC tissues can reflect the degree of tumor malignancy, invasion, and metastasis, and are closely related to the formation of microvessels in tumor tissues and the poor prognosis of patients.
Clinical • Journal
|
VEGFA (Vascular endothelial growth factor A)
|
CD73 expression
almost2years
Prognostic impact of CD73 expression and its relationship to PD-L1 in patients with radically treated pancreatic cancer. (PubMed, Virchows Arch)
In multivariate analysis, CD73 positivity in tumour cells was an independent negative prognostic factor together with histopathological grade, TNM stage, and low immune cell score. In conclusion, high CD73 expression in tumour cells is associated with poor survival in PDAC independently of the number of tumour-infiltrating lymphocytes or TNM stage.
Clinical • Journal • PD(L)-1 Biomarker
|
PD-L1 expression • CD73 overexpression • CD73 expression • TILs
almost2years
CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer. (PubMed, J Cell Mol Med)
In conclusion, these results reveal that CD73 may function as a promotor in cancer progression and a regulator in immune patterns via CD73-related pathways. Blockade of CD73 might be a promising therapeutic strategy for PC.
Journal • Tumor Mutational Burden • PD(L)-1 Biomarker
|
TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8)
|
PD-L1 expression • CD73 expression • TMB + PD-L1 expression
almost2years
Cervical cancer cells produce TGF-β1 through the CD73-adenosine pathway and maintain CD73 expression through the autocrine activity of TGF-β1. (PubMed, Cytokine)
TGF-β1 produced by CeCa cells was necessary to maintain CD73 expression because the addition of anti-TGF-β neutralizing antibodies or the inhibition of TGF-βRI strongly reversed the expression of CD73 in the CeCa cells. These results suggested a feedback loop in CeCa cells that favors immunosuppressive activity through the production of TGF-β1 and Ado as well as the autocrine activity of TGF-β1 and expression of CD73.
Journal
|
CD73 expression
2years
The distinct role of CD73 in the progression of pancreatic cancer. (PubMed, J Mol Med (Berl))
TNFR2 was involved in CD73-induced AKT and ERK signaling pathway. miR-30a-5p targeted CD73 and increased the sensitivity to gemcitabine.
Journal
|
TNFA (Tumor Necrosis Factor-Alpha)
|
CD73 expression
|
gemcitabine
2years
CD8+CD73+ T cells in the tumor microenvironment of head and neck cancer patients are linked to diminished T cell infiltration and activation in tumor tissue. (PubMed, Eur J Immunol)
In vitro studies with peripheral blood T cells indicate that anti-CD3-stimulation causes loss of CD73 expression, especially among cells that undergo proliferation and that exogenous AMP can impair T cell proliferation, while sustaining CD73 expression. These data suggest that CD8+CD73+ T cells may be especially important mediators of immunosuppression in human head and neck cancer.
Clinical • Journal
|
CD8 (cluster of differentiation 8)
|
CD8 expression • CD73 expression
2years
ALCAM (CD166) as a gene expression marker for human mesenchymal stromal cell characterisation. (PubMed, Gene X)
A total of six other genes (ALCAM, CLIC1, EDIL3, EPHA2, NECTIN2, and TMEM47) were identified as possible biomarkers for accurate identification of MSCs. Justified by considerations on expression level, reliability and specificity, Activated-Leukocyte Cell Adhesion Molecule (ALCAM) was the best candidate for improving the biomarker set of MSC identification.
Journal
|
EPHA2 (EPH receptor A2)
|
CD73 expression
2years
NT5E is associated with unfavorable prognosis and regulates cell proliferation and motility in gastric cancer. (PubMed, Biosci Rep)
Moreover, silencing of Ecto-5'-nucleotidase expression suppressed cell proliferation, migration and invasion in vitro in gastric cancer. In conclusion, Ecto-5'-nucleotidase is a credible prognostic biomarker, and serves as a potential therapeutic target in gastric cancer.
Journal
|
CD73 expression
2years
Adenosine Generated by Regulatory T Cells Induces CD8 T Cell Exhaustion in Gastric Cancer through A2aR Pathway. (PubMed, Biomed Res Int)
The FoxP3 Tregs and A2aR/CD8 T cells were excessively infiltrated in GC tissue. Tregs from GC can decompose ATP to adenosine and in turn induce apoptosis and inhibit the proliferation of CD8 T cells through the A2aR pathway, further leading to immune escape of GC.
Journal
|
CD8 (cluster of differentiation 8) • FOXP3 (Forkhead Box P3)
|
CD73 expression • FOXP3 expression
2years
A novel proangiogenic B cell subset is increased in cancer and chronic inflammation. (PubMed, Sci Adv)
In addition, tissue-infiltrating IgG4CD49bCD73 B cells expressing proangiogenic cytokines were detected in patients with EoE and melanoma. Our results demonstrate a previously unidentified proangiogenic B cell subset characterized by expression of CD49b, CD73, and proangiogenic cytokines.
Journal
|
VEGFA (Vascular endothelial growth factor A)
|
CD73 expression
2years
Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade. (PubMed, J Immunother Cancer)
Our data suggest that the adenosine pathway can be successfully targeted in MM and blocking this pathway could be an alternative to PD1/PDL1 inhibition for MM and other hematological cancers. Inhibitors of the adenosine pathway are available. Some are in clinical trials and they could thus reach MM patients fairly rapidly.
Journal • PD(L)-1 Biomarker
|
IFNG (Interferon, gamma)
|
CD73 expression
|
imaradenant (AZD4635)
2years
[VIRTUAL] Determinants of immune evasion in MET driven lung cancer (AACR-II 2020)
MET altered tumors and LC cell lines express high levels of CD73 and other adenosinergic-related molecules, representing a potential mechanism of immune evasion and target for immunotherapy. The potential predictive role of CD73 expression in a larger cohort of patients treated with immune checkpoint inhibition (ICI) will be performed.
PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1)
|
MET amplification • MET exon 14 mutation • MET expression • CD73 expression
2years
[VIRTUAL] Anti-PD-L1 and anti-CD73 combination therapy promotes T cell response to EGFR mutant NSCLC (AACR-II 2020)
The combination therapy also increased the frequency of CD62L+CD45RO+CCR7+ phenotype in CD8+ T cells in the spleen compared to isotype control (~120%, p<0.001), but not in the tumor, as well as enhancing IFNγ production by tumor antigen-specific CD8+ T cells compared to isotype control (~224%, p<0.001). Together, these results further support the ongoing clinical trials evaluating combination of anti-CD73 and anti-PD-L1 in treating EGFR mutant NSCLC while suggesting the increased central memory T cells may play a role in response to therapy.
Combination therapy • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • GZMB (Granzyme B)
|
EGFR mutation • CD73 expression
2years
[VIRTUAL] Characterization of immune cell biomarkers in undifferentiated pleomorphic sarcoma (AACR-II 2020)
In this study, we characterized the immune cell infiltrates and the expression of PD-L1, pSTAT3, CD73 and CD39 in UPS. These biomarkers differentially correlated with clinicopathological characteristics in primary, recurrent and metastatic tumors. Lower TILs and low CD73/PD-L1 expression were associated with inferior survival outcomes.
PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD163 (CD163 Molecule)
|
PD-L1 expression • CD73 expression
2years
[VIRTUAL] A next-gen anti-CD73 Antibody with potential to show better efficacy and safety profile than existing approach (AACR-II 2020)
Both enzymatic and non-enzymatic dependent functions of CD73 were significantly dampened. The antibody demonstrates a superior anti-tumor activity over reference antibodies in in-vitro and in-vivo models.Our findings indicate that the antibody has promising potential as an effective therapy for PD-1/PD-L1 nonresponsive or refractory patients, as well as a broader patient population that may benefit from a unique mechanism of action of CD73-targeting antibody.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
CD73 overexpression • CD73 expression
2years
[VIRTUAL] Inhibiting adenosine signaling and KRAS enhances the effect of α-PD-1 therapy in a KRASG12C/TP53R172H/+ pancreatic cancer model (AACR-II 2020)
C57BL/6J mice bearing established KP4662-G12C (KRASG12C/TP53R172H/+) tumors (at least 150 mm3) were treated as indicated: A1421 (CD73i; 30 mg/kg/day, s.c.), anti-PD1 (Clone RMP 1-14; 10 mg/kg; twice per week, i.p), and MRTX-1257 (KRASi, 100 mg/kg/day, p.o.)... Here, we show that direct inhibition of mutant KRAS in pancreatic cancer models yields complex immunomodulatory effects. While antigen presentation pathways are transcriptionally upregulated and the expression of immunosuppressive chemokine is reduced, KRAS inhibition also reprograms nucleotide metabolism leading to elevated levels of ADO. These findings suggest that co-targeting mutant KRAS and adenosine signaling may enhance immunotherapy against pancreatic cancer and potentially other KRAS driven malignancies.
Preclinical • PD(L)-1 Biomarker • IO biomarker
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12 • CD73 expression • KRAS expression
|
MRTX1257
2years
CD73 blockade enhances the local and abscopal effects of radiotherapy in a murine rectal cancer model. (PubMed, BMC Cancer)
These results suggest that adenosine plays an important role in the anti-tumor effects mediated by RT and that CD73/adenosine axis blockade may enhance the anti-tumor effect of RT, and improve the outcomes of patients with locally advanced rectal cancer.
Preclinical • Journal
|
CD73 expression
2years
Natural Killer Cells Engineered to Target Adenosingeric Immunometabolic Suppression as an Immunotherapy Against Lung Carcinoma (ASGCT 2020)
The TME is highly immunosuppressive via the activity of CD73 and accumulation of adenosine. Therefore, to redirect NK cell function, a novel NK-specific anti-CD73 targeting construct is being pursued as a promising adoptive immunotherapy to prevent tumor growth of CD73+ lung adenocarcinoma, which is potentially extendable to other CD73-expressing tumors.
IO biomarker
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IFNG (Interferon, gamma) • IL2 (Interleukin 2) • NKG2D (killer cell lectin like receptor K1)
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CD73 expression
2years
Prognostic value of CD73 expression in resected colorectal cancer liver metastasis. (PubMed, Oncoimmunology)
Patients with high levels of sCD73 also had shorter disease-specific survival. Our results suggested that CD73 in CRLMs may be prognostically informative and may help select patients more likely to respond to adenosine pathway blocking agents.
Journal
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CD73 expression
2years
Differential expression of CD73, CD86 and CD304 in normal vs. leukemic B-cell precursors and their utility as stable minimal residual disease markers in childhood B-cell precursor acute lymphoblastic leukemia. (PubMed, J Immunol Methods)
Here we show that CD73, CD86 and CD304 are aberrantly (over)expressed in a substantial percentage of BCP-ALL patients and that their expression profile remains relatively stable early after starting therapy, supporting their potential contribution to improved MRD analysis by flow cytometry.
Clinical • Journal
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ETV6 (ETS Variant Transcription Factor 6) • NRP1 (Neuropilin 1)
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CD73 expression
2years
Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73+γδ1 Treg cells. (PubMed, Signal Transduct Target Ther)
Our results showed that the BC-derived exosomal SNHG16/miR-16-5p/SMAD5-regulatory axis potentiates TGF-β1/SMAD5 pathway activation, thus inducing CD73 expression in Vδ1 T cells. Our results first identify the significance of CD73+Vδ1 Tregs in BC, and therapy targeting this subpopulation or blocking TDEs might have potential for BC treatment in the future.
Journal
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CD73 expression
2years
[VIRTUAL] Role for the ectonucleotidase CD39: Outcome and association with PD-1/PD-L1 based cancer immunity in clear cell renal cell carcinoma (AUA 2020)
Ectonucleotidase CD39 expression levels may be a new biomarker for ccRCC prognosis. Further, for the first time we reveal a relationship between cancer immunity and adenosine signaling in ccRCC, promoting a rational combination immunotherapy strategy in future clinical practice. Source of Funding: None.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8)
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PD-L1 expression • PD-1 expression • CD73 expression