CD73 expression

When quercetin and luteolin were combined with the chemotherapeutic paclitaxel in a triple-drug regimen, we found an effective downregulation in paclitaxel-enhanced CD73 and CSC-promoting pathways YAP and Wnt...Conclusively, our findings elucidate the significance of CSCs in impairing anti-tumor immunity. The high efficacy of our triple-drug regimen in clinically relevant platforms not only underscores the importance for further mechanistic investigations but also paves the way for potential development of new, safe, and cost-effective therapeutic strategies for TNBC.

P2, N=0, Withdrawn, TJ Biopharma Co., Ltd. | N=160 --> 0 | Trial completion date: Dec 2024 --> Dec 2023 | Suspended --> Withdrawn | Trial primary completion date: Jun 2024 --> Dec 2023

STOM, CCBE1, and LAMA5 were highly expressed in tumor-derived MPCs, with STOM being found to retard the proliferation of MPCs but promote the proliferation of BC cells. There findings present new possibilities in targeted microenvironmental therapy for BC.

The highly expressed CD38 converts NAD + to adenosine through the CD203a/CD73 complex and adenosine binds and activates its receptor A2AR, inducing the expression of Snail and promoting the invasion and metastasis of lung cancer cells. This finding elucidates a new perspective on the interplay between NAD + metabolism and glycolysis in tumor development.

Furthermore, the combination of STING agonist and anti-CD73 mAb markedly blocked tumor growth in vivo by promoting the infiltration of CD8+ T cells and reducing the accumulation of Foxp3+ regulatory T cells (Tregs) in the tumor microenvironment. Our work provides a rationale for the combination of STING agonists and CD73 inhibitors in cancer immunotherapy.

In preclinical models of TNBC, ST80 treatment sensitized refractory tumors to anti-PD-L1 therapy. Collectively, our findings uncover a novel strategy for targeting immunosuppressive OTUD4-CD73 proteolytic axis in treating immune-suppressive breast cancers with the inhibitor ST80.

Several antagonistic adenosine-targeting biological therapies that decrease the suppressive action of tumor-associated macrophages have been produced and explored to transform this result from basic research into a therapeutic advantage. Here, we'll review the newest findings from studies of pharmacological compounds that target adenosine receptors, and their potential therapeutic value based on blocking the suppressive action of macrophages in tumors.

Our study reveals a hypoxia-mediated alteration of the CD39/CD73 axis in OSA patients, which could trigger ADO upregulation, thus potentially contributing to the immune suppressive environment and ultimately facilitating tumor development and progression. Therefore, our data highlights the need for new longitudinal studies evaluating CD39 and/or CD73 as potential cancer-risk prognostic biomarkers in OSA patients.

These findings indicate that ZIKV infection could lead to reduced cell viability, elevated CD73 expression, improved cellular adherence, and higher rates of apoptosis in glioblastoma cells. Further studies are required to explore the potential use of ZIKV in the treatment of GBM.

DHA supplementation may be utilized in breast cancer therapy for down-regulation of cellular and exosomal immune escape-related molecules.

Collectively, our findings suggest an association between CD73 expression and/or activity and the post-transcriptional regulation of ZEB1 by non-coding RNA, indicating a reduction in its absence. Further investigations are warranted to elucidate the relationship between CD73 and ZEB1, with the potential for targeting them as therapeutic alternatives for cancer treatment in the near future.

For the first time, we have achieved the construction of a scaffold-free, bone-like luminal structure through the assembly of spheroids comprised of this hGMSCs. This success is sure to be close to the induction of clinical application against regenerative medicine especially for bone defect disease.

The in vivo senescence model was induced by 8 Gy×3 radiotherapy or cisplatin chemotherapy, and the in vitro model was induced by 10 Gy-irradiation or cisplatin treatment...Lastly, blocking CD73 in a senescent background suppresses tumors and activates CD8+ T cell-mediated antitumor immunity. TAMs expressed CD73 contributes significantly to the adenosine accumulation in the senescent TME, suggesting targeting CD73 is a novel synergistic anti-tumor strategy in the aging microenvironment.

Clinical scale manufacturing using INO generated enhanced potency CAR-T cell products meeting criteria for clinical dosing. These results identify INO as a potent modulator of CAR-T cell metabolism and epigenetic stemness programming and deliver an enhanced potency platform for cell manufacturing.

The LGR5+-derived tumors exhibited a highly vascularized stroma with substantial fibrosis. In addition, we identified pro-angiogenic factors and signaling pathways involved in neo-angiogenesis and vascular development, which represent potential new targets for anti-angiogenic strategies to overcome tumor resistance to current ICC treatments.

These results demonstrate that the catalytic activity of CD73 contributes to the pathogenic growth of FN-RMS through the activation of the purinergic signaling pathway. Therefore, targeting CD73 and the purinergic signaling pathway represents a potential therapeutic approach for FN-RMS patients.

Taken together, the present study demonstrates a role of NK cells in the aggravation of uveal melanoma towards metastatic disease.

CD73 and A2aR expression correlated with the poorest prognosis group among S/R RCCs, indicating that the use of inhibitors against them in combination with conventional therapies may improve prognosis.

In a culture of peripheral blood mononuclear cells isolated from the blood of 5 healthy donors, ADK did not abolish the inhibitory effect on the expression of CD39 and CD73 by CD8T cells in the presence of a high concentration of ATP (a source for ADO). Effects on CD39CD4, CD73CD4T cells and CD39 Treg cells were also not found.

It explores roles within tumor cells, the lung's stromal environment, and the immune system. Ranging from pre-clinical models to clinical trials, potential therapies targeting the adenosine pathway for lung cancer treatment are discussed below.

Cells from passages 13 to 23 possessed the ability to differentiate into adipocytes, osteoblasts, and chondrocytes; after passage 23, their ability to form these cell types was lost. These data indicate that the cells that formed the AGMK1-9T7 cell line were GLI1+ perivascular, kidney, progenitor cells.

Results from ARC-8 demonstrate the addition of Q 100 mg ± Z to G/nP was safe and tolerable, with no significant added toxicity to GnP. Modulation of eADO with Q may confer benefit beyond radiographic measures of disease. The OS is promising and supports further development of Q in mPDAC.

This study identifies distinct somatic mutations in AML patients' MSC and leukemic cell fractions, revealing genomic complexity and crosstalk impacting leukemia progression. Understanding the functional implications of these mutations is crucial for unraveling their roles in leukemogenesis and developing personalized therapeutic interventions targeting MSC somatic mutations.

Furthermore, our results demonstrated positive correlations between ADP hydrolysis and the transurethral resection and Gleason score. Understanding the role of ectonucleotidases is crucial for identifying new biomarkers in PC.

Our study has implicated that lower CD26 expression on immune cell subtypes of the donor stem cell harvest is associated with reduced risk of GVHD and better survival. The underlying mechanism was found to be through NF-κB pathway and pro-inflammatory cytokines. Based on these observations, chemically designed or natural resources-based CD26 inhibitors can be explored further in clinical trials for improving ASCT outcomes.

We found that knocking down the expression of CD73 in NPC cells could inhibit cells malignant phenotype. Collectively, CD73 plays important roles in NPC malignant behavior and might act as a novel target for the diagnosis and treatment of NPC.

We optimized an mIF panel for detection of markers in the adenosine pathway, an emerging clinically relevant pathway. The densities and spatial distribution demonstrated that this pathway may modulate aspects of the tumor immune microenvironment.

To further demonstrate the role of PD-L1, we treated the PDL1-high expression cells MDA-MB-231, PD-L1 silenced MDA-MB-231 clones, and PD-L1 low expression cells MCF-7 with Durvalumab, an anti-PD-L1...Here, we further characterized the cellular autonomic role of PD-L1 in breast cancer and showed a differential role of basal PD-L1 expression in PD-L1 checkpoint inhibitors treatment efficacy. This suggests a potential role in monitoring PD-L1 expression indirect biomarkers (i.e. miR-320a, miR-145 and CD73) during ICIs treatment.

We report for the first time an enrichment of DN cells in breast cancer tumour tissue, specifically the expansion of DN2 cells following neoadjuvant chemotherapy. Functional analyses of tumour-infiltrated B-cells suggest that mechanistically, these B-cell subgroups may contribute to immunosurveillance and point to an important role of purinergic signalling in early breast cancers. Our study highlights the requirement for further investigation into the role of DN B cells in the context of chemo/immunotherapy resistance in breast cancers.

STUDY DESIGN AND METHODS Objectives and endpoints: Primary objective: To evaluate the safety and feasibility of FP-1201 in patients undergoing treatment with axi-cel or brexu-cel with two co-primary endpoints: i) to estimate the incidence of dose-limiting toxicity rates within the first 14 days following the last administration of FP-1201; ii) to study the type, frequency, and severity of adverse events according to the NCI CTCAE v5.0 from the first administration of FP-1201 and until day +28 after CAR T-cell infusion Secondary objectives: i) To decrease the incidence and severity of ICANS; ii) to decrease the incidence and severity of CRS; iii) to decrease corticosteroid usage; iv) to evaluate the effect of FP-1201 on anti-tumor efficacy Exploratory objectives: To characterize the in vivo effects of FP-1201 on endothelial function, the systemic cytokine milieu, and CAR T-cell function Key inclusion criteria: Adults ≥18 years of age with Karnofsky performance status ≥60% and B-cell non-Hodgkin lymphoma eligible for treatment with axi-cel or brexu-cel Key exclusion criteria: Known hypersensitivity to IFN-beta or major organ dysfunction FP-1201 administration: The FDA-approved IFN-beta-1a Rebif® will be formulated for IV administration (FP-1201). The aim is to demonstrate safety and efficacy and to investigate the biologic mechanisms of IFN-beta-1a in preventing endothelial dysfunction. Additional preclinical and preliminary clinical data will be presented at the meeting.

The findings of this study highlight the interplay among PD-L1, CD73, A2AR, CTLA-4, and PD-1 in colorectal cancer. They suggest that high expression of PDL1 may contribute to tumor progression through suppressing the immune response, whereas CD73 and A2AR may play a role in tumor aggressiveness and metastasis. In addition, the positive correlation between CTLA-4 and PD-1 expression in TILs suggests potential synergistic effects in modulating the anti-tumor immune response.

In summary, FL-PDLS is a robust patient-derived 3D system that can be used as a tool to mimic FL pathology and to test novel immunotherapeutic approaches in a context of personalized medicine.

Moreover, combined blockade of TIGIT and CD47 significantly increased phagocytosis of ovarian cancer cells by TAMs in comparison to a single blockade of CD47. Combined blockade of TIGIT and CD47 represents a promising approach to enhance anti-CD47-facilitated phagocytosis.

This study suggests that CAF-FA-CS-NPs (D4) in combination with MTX may be a promising candidate for cancer immunotherapy, by inhibiting A2aR signaling and leading to improved immune activation and anti-tumor activity of MTX.

Median age was 59 years (range 38-84 years), and the majority of the patients presented with high-grade serous carcinoma (HGSC, 85.4%) and stage III-IV disease (89.6%) at diagnosis. Among the treatment-naive patients, 17.1% of patients (n=6) showed low CD73 expression (grade 1), whereas 60.0 % of patients (n=21) showed high CD73 expression (grade 2/3). All of the BRCA1/2-mutated tumors were high CD73 (n=7), whereas 20% of BRCA1/2-non-mutated tumors (n=5) were low CD73 expression.

Tissue microarrays of human PDAC biopsies combined with bioinformatic analysis reveal that rounded-amoeboid invasive cells with high CD73-ROCK-Myosin II activity and their immunosuppressive microenvironment confer poor prognosis to patients. We propose targeting amoeboid PDAC cells as a therapeutic strategy.

We also found that CD73 deletion inhibited the ERK/STAT3 pathway and activated the E-cadherin pathway. In addition, a CRISPR/Cas9 protein kinase library screen was performed and identified Pbk, Fastk, Cdk19, Adck5, Trim28, and Pfkp as possible genes regulating CD73.

Moreover, hPMSCs enhanced Nrf2 expression and diminished Fyn expression via the CD73/ADO pathway in Th1, TNF-α, and IL-10 cells. These results indicated that hPMSCs promoted and inhibited the secretion of IL-10 and TNF-α, respectively, during Th1 cell differentiation through the CD73/ADO/Fyn/Nrf2 axis signaling pathway, thereby alleviating liver tissue injury in GVHD mice.

Utilizing lactate generation inhibitor not only reprogramed glucose metabolism of cancer stem cells, but also alleviated immunosuppression of tumor microenvironment and reduced tumor-infiltrating CAR-Treg cells, which may be a potential strategy to enhance CAR-T function in glioblastoma therapy.