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BIOMARKER:

PD-L1 underexpression

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Other names: PD-L1, CD274, HPD-L1, PD-L1, B7H1, PDL1, Programmed death ligand 1, B7-H1, B7-H, PDCD1L1, PDCD1LG1, PDCD1 Ligand 1, B7 homolog 1, CD274 Antigen, Programmed cell death 1 ligand 1, CD274 molecule
Entrez ID:
Related biomarkers:
15d
Bempegaldesleukin plus nivolumab in first-line advanced/metastatic urothelial carcinoma: Results from a phase II single-arm study (PIVOT-10). (PubMed, Urol Oncol)
BEMPEG plus NIVO did not meet the efficacy threshold for ORR in patients with previously untreated locally advanced or metastatic urothelial carcinoma and low PD-L1 expression.
P2 data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • IL2 (Interleukin 2)
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PD-L1 expression • PD-L1 underexpression • PD-L1-L
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Opdivo (nivolumab) • bempegaldesleukin (NKTR-214)
24d
The prognostic and therapeutic value of the tumor microenvironment and immune checkpoints in pancreatic neuroendocrine neoplasms. (PubMed, Sci Rep)
The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.
Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • CD163 (CD163 Molecule) • CD4 (CD4 Molecule) • CD69 (CD69 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • CD68 (CD68 Molecule) • GZMB (Granzyme B) • FOXP3 (Forkhead Box P3)
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PD-L1 expression • PD-L1 underexpression • PD-1 expression • CD163 expression • FOXP3 expression
28d
The tumor immune microenvironment of SCLC is not associated with its molecular subtypes. (PubMed, Eur J Cancer)
SCLC TME is highly heterogeneous. Immune-hot tumors were associated with OS but not with molecular classification. PD1 expression and PD-L1 expression by immune cells may thus serve as a prognostic marker.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • YAP1 (Yes associated protein 1) • CD4 (CD4 Molecule) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) • NEUROD1 (Neuronal Differentiation 1)
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PD-L1 expression • PD-L1 overexpression • PD-L1 underexpression • PD-1 expression
1m
Pepinemab a semaphorin 4D blockade antibody in combination with immune checkpoint therapies induces mature lymphoid aggregates correlating with clinical outcomes (SITC 2024)
The KEYNOTE-B84 study (NCT04815720) evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC. Biomarker studies conducted in patients with surgically resectable metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) received neoadjuvant treatment with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone...Increased density and maturity of lymphoid aggregates correlated with disease control and longer progression-free survival (PFS). Conclusions Pepinemab, a Semaphorin 4D (SEMA4D) blocking antibody, in combination with ICB converts 'Cold' tumors to 'Hot' by inducing organized lymphoid aggregates.
Combination therapy • Clinical data • Clinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CXCR5 (C-X-C Motif Chemokine Receptor 5) • SEMA4D (Semaphorin 4D)
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PD-L1 underexpression • PD-L1 negative • PD-L1-L • CXCR5 expression
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Sema4 Signal®
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab) • pepinemab (VX15)
1m
Cancer cell-specific PD-L1 expression is a predictor of poor outcome in patients with locally advanced oral cavity squamous cell carcinoma. (PubMed, J Immunother Cancer)
Our findings underscore the prognostic significance of PD-L1 expression in locally advanced OCSCC, and unveil the complex interplay between PD-L1 expression, immune responses, and molecular pathways in the tumor microenvironment. This study provides insights that may inform future therapeutic strategies, including the possibility of tailored immunotherapeutic approaches for patients with PD-L1hi locally advanced OCSCC.
Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD68 (CD68 Molecule) • ITGAX (Integrin Subunit Alpha X)
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PD-L1 expression • PD-L1 underexpression
1m
Integrated analysis to identify biological features and molecular markers of poorly cohesive gastric carcinoma (PCC). (PubMed, Sci Rep)
Initial molecular characterization of these PCC components revealed distinct features, including low expression of claudin-3, -4, and -7, high expression of IGFBP7, and the presence of PD-L1. These molecular traits may partially account for the pronounced tumor heterogeneity observed in GC.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • IGFBP7 (Insulin Like Growth Factor Binding Protein 7) • CLDN3 (Claudin 3)
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PD-L1 expression • PD-L1 underexpression
2ms
Molecular diagnostic characteristics in non-small cell lung carcinomas (NSCLC) and its relationship with the PD-L1 expression (ECP 2024)
Our study showed the heterogeneity in PD-L1 expression with respect to major oncogenic drivers in Turkey. KRAS, BRAF, MET mutations and ALK and ROS1 rearrangements were more frequent, while EGFR and HER2 mutations were less frequent compared with the overall PD-L1 expression levels. Molecular testing of non-small cell lung carcinomas (NSCLC) for oncogenic driver mutations has become standard in pathology practice.
PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • HER-2 mutation • PD-L1 underexpression • ALK rearrangement • MET exon 14 mutation • PD-L1 negative • ROS1 rearrangement • MET mutation
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VENTANA PD-L1 (SP263) Assay
2ms
Inhibition of Semaphorin 4D induces lymphoid aggregates, correlating with clinical outcomes when combined with immune checkpoint therapy (CRI-ENCI-AACR ICIC 2024)
Screening and on-treatment tumor biopsies were collected from several clinical trials: the KEYNOTE-B84 study (NCT04815720), that evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC, and biomarker neoadjuvant studies conducted in metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) patients with surgically resectable disease treated with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone. When SEMA4D is blocked from binding to its receptors, suppression is reduced, leading to increased penetration and organization of antigen presenting cells (APC) and lymphoid cells in the tumor microenvironment. It is expected that this would facilitate interaction and communication among these cell populations, accounting for improved immune responses in otherwise "cold" tumors.
Clinical data • Clinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CXCR5 (C-X-C Motif Chemokine Receptor 5) • SEMA4D (Semaphorin 4D)
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PD-L1 underexpression • PD-L1-L • CXCR5 expression
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Sema4 Signal®
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab) • pepinemab (VX15)
2ms
Genomic profiles and immune microenvironment of olfactory neuroblastoma (PubMed, Zhonghua Bing Li Xue Za Zhi)
The low expression of PD-L1 and the low percentage of CD8+ TIL indicate that ONB might not be sensitive to immunotherapy. The percentage of M1-type macrophages in low-grade ONB is significantly higher than that in high-grade ONB, suggesting that M1-type macrophages may be involved in the progression of ONB from low-grade to high-grade.
Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CD163 (CD163 Molecule) • CD68 (CD68 Molecule) • ZNRF3 (Zinc And Ring Finger 3)
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PD-L1 expression • PD-L1 underexpression
4ms
Evaluation of the Immune Landscape of Patients with Adenosquamous NSCLC (LUAS) (IASLC-WCLC 2024)
This suggests that additional factors beyond the immune environment may also influence immunotherapy responses in LUAS, highlighting the need for further investigation. Table 1: Genomic/Immune landscape of LUAS, AC, SCC along with LUAS primary and metastatic sites Adenosquamous (LUAS, n =374) Squamous (SCC, n = 9635) Adenocarcinoma (AC, n = 25665) p-value (SCC vs LUAS) p-value (AC vs LUAS) Overall Actional Alteration Prevalence EGFR, ALK, ROS1, RET fusions /rearrangements, METex14, BRAF V600E, KRAS G12C, NTRK fusions, HER2 110 (29.4%) 343 (3.67%) 9267 (36.22%) 1%) 228 (65.5%) 5293 (59.8%) 12789 (53.7%) 0.033 50%) 110 (31.6%) 2119 (26.3%) 6218 (31.2%) 0.0293 0.1843 PD-L1 low (1-49%) 112/348 (33.9%) 3009/8045 (37.8%) 6177/20023 (30.8%) 0.048 0.512 No PDL1 (0%) 126/348 (36.2%) 2917/8045 (35.9%) 7628/20023 (38.1%) 0.984 0.3621 TMB High ( > 10 Mut/MB) 112 (30.6%) 3488 (38.47%) 8159 (32.94%) 0.002 0.344 Tumor microenvironment LUAS Median cell fraction (%) SCC Median cell fraction (%) AC Median cell fraction (%) p-value (SCC vs LUAS) p-value (AC vs LUAS) Monocytes 0.02 0.06 0.10 0.138 0.017 T cells CD4 0.04 0.07 0.11 0.274 0.130 Neutrophils 5.57 5.23 4.85 0.165 0.020 NK cells 2.68 2.49 2.94 0.005 <0.001 T cells CD8 0.39 0.11 0.27 <0.001 0.164 Macrophages M2 6.08 4.65 6.19 <0.001 0.172 Macrophages M1 4.57 2.64 5.12 <0.001 0.005 B cells 4.08 4.19 3.87 0.092 0.160 Dendritic cells 0.61 1.07 0.54 <0.001 0.049 Tregs 2.92 1.75 2.76 <0.001 0.365 Immune-related genes LUAS Median Gene expression median ((Log2 (TPM+1)) SCC Median Gene expression median ((Log2 (TPM+1)) AC Median Gene expression median ((Log2 (TPM+1)) p-value (SCC vs LUAS) p-value (AC vs LUAS) PDCD1LG2 1.447 1.319 1.284 0.009 <0.001 PDCD1 0.817 0.711 0.790 0.003 0.251 CTLA4 1.914 1.629 1.638 <0.001 0.001 CD86 3.534 3.218 3.482 <0.001 0.337 ID01 2.850 2.300 2.241 <0.001 <0.01 CD274 3.210 3.122 3.031 0.717 0.132 CD80 2.888 2.569 2.798 <0.001 0.453 HAVCR2 4.511 3.999 4.499 <0.001 0.739 LAG3 1.037 1.043 0.865 0.466 0.001 IFNG 0.841 0.697 0.691 0.026 0.025
Clinical • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD4 (CD4 Molecule) • NTRK (Neurotrophic receptor tyrosine kinase) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
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PD-L1 expression • BRAF V600E • KRAS G12C • BRAF V600 • RET fusion • PD-L1 underexpression • ROS1 fusion • RET rearrangement • KRAS G12 • KRAS G12C + PD-L1 expression • PD-L1-L • NTRK fusion
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PD-L1 IHC 22C3 pharmDx
7ms
Human epidermal growth factor receptor-2 expression and subsequent dynamic changes in patients with ovarian cancer. (PubMed, Sci Rep)
Patients with HER2-overexpressing OC exhibited distinct histological, IHC, and genomic profiles. HER2-targeting agents are potential options for BRCA-wildtype patients, particularly as later lines of treatment.
Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ARID1A (AT-rich interaction domain 1A) • BRCA (Breast cancer early onset)
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PD-L1 expression • TP53 mutation • KRAS mutation • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • PD-L1 underexpression • ARID1A mutation • BRCA wild-type • TP53 expression • BRCA mutation • HER-2 amplification + PD-L1 expression • PD-L1-L
8ms
Enrollment open • Combination therapy • Metastases
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 underexpression • PD-L1-L
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Keytruda (pembrolizumab) • WM-A1-3389
8ms
PD-L1 on large extracellular vesicles is a predictive biomarker for therapy response in tissue PD-L1-low and -negative patients with non-small cell lung cancer. (PubMed, J Extracell Vesicles)
Patients with high baseline levels of PD-L1+ lEVs in blood showed a significantly better response to immunotherapy and prolonged survival. This was particularly true in the subgroup of NSCLC patients with low or absent tPD-L1 expression, thus identifying PD-L1-positive lEVs in plasma as a novel predictive and prognostic marker for immunotherapy.
Journal • PD(L)-1 Biomarker • IO biomarker
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PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • SELP (Selectin P)
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PD-L1 expression • PD-L1 underexpression • PD-L1-L
8ms
Association of PD-L1 expression with driver gene mutations and clinicopathological characteristics in non-small cell lung cancer: A real-world study of 10 441 patients. (PubMed, Thorac Cancer)
PD-L1 expression was associated with well-defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD-L1 in patients with advanced NSCLC in a large Latin American cohort.
Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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PD-L1 expression • PD-L1 overexpression • KRAS G12C • ALK positive • PD-L1 underexpression • PD-L1 negative • KRAS G12 • EGFR positive • KRAS G12C + PD-L1 expression • PD-L1-L
9ms
An exosome-derived lncRNA signature identified by machine learning associated with prognosis and biomarkers for immunotherapy in ovarian cancer. (PubMed, Front Immunol)
Patients with low expression of PDL1 or high expression of CTLA4 and low ERLS exhibited significantly better survival prospects, whereas patients with high ERLS and low levels of PDL1 or CTLA4 exhibited the poorest outcomes. Our study constructed an ERLS model that can predict prognostic risk and immunotherapy response, optimizing clinical management for OC patients.
Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Machine learning
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
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PD-L1 expression • TMB-H • PD-L1 overexpression • PD-L1 underexpression • CTLA4 expression
9ms
Programmed Death-Ligand 1 (PD-L1) Expression in Penile Squamous Cell Carcinoma - A Comparative Assessment of the Reference Clone 22C3 with SP263 and E1L3N Clones along with a Correlation of Clinicopathologic and Survival Parameters (USCAP 2024)
1. Ours is the first study to demonstrate that SP263 and E3L1N can reliably be used to evaluate PD-L1 in PCs as there is good concordance with the reference clone 22C3. 2.
Clinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 overexpression • PD-L1 underexpression • PD-L1 negative • CDKN2A negative • PD-L1-L
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PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
10ms
Integrative analysis of the cuproptosis-related gene ATP7B in the prognosis and immune infiltration of IDH1 wild-type glioma. (PubMed, Gene)
In conclusion, our research constructed a prognostic cuproptosis-related gene signature model to predict the prognosis of IDH1 wild-type glioma. ATP7B is deemed to be a potential prognostic indicator and novel immunotherapy biomarker for IDH1 wild-type glioma patients.
Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CD8 (cluster of differentiation 8)
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PD-L1 overexpression • PD-L1 underexpression • IDH wild-type
10ms
High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors in triple-negative breast cancer. (PubMed, NPJ Breast Cancer)
In addition, patients with B7-H3 high and PD-L1 low expression showed the lowest anti-tumor immune infiltration, the highest collagen level, and the lowest therapeutic responses to multiple therapies, which mostly belong to armored-cold tumors. Overall, this research provides a novel subtyping strategy based on the combination of B7-H3/PD-L1 expression, which leads to a novel approach for the management of TNBC.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD276 (CD276 Molecule)
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PD-L1 expression • PD-L1 underexpression • CD276 expression • PD-L1-L
10ms
Reconstruction of unreported subgroup survival data with PD-L1-low expression in advanced/metastatic triple-negative breast cancer using innovative KMSubtraction workflow. (PubMed, J Immunother Cancer)
ICI-based regimens are not associated with a survival benefit versus chemotherapy in subgroups of advanced/metastatic TNBC that express low PD-L1 levels.
Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 underexpression • PD-L1-L
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Keytruda (pembrolizumab)
10ms
Exploring the Cost Effectiveness of a Whole-Genome Sequencing-Based Biomarker for Treatment Selection in Patients with Advanced Lung Cancer Ineligible for Targeted Therapy. (PubMed, Pharmacoeconomics)
The use of WGS-TMB is not cost effective compared to PD-L1 for immunotherapy treatment selection in non-squamous metastatic non-small cell lung cancer in the Netherlands. WGS-TMB could become cost effective provided there is a reduction in the cost of WGS testing or there is an increase in the predictive value of WGS-TMB for immunotherapy effectiveness. Alternatively, a combination strategy of PD-L1 testing with WGS-TMB would be cost effective if used to support the choice to withhold immunotherapy in patients with a low expected benefit of immunotherapy.
Journal • HEOR • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Cost-effectiveness • Cost effectiveness • Metastases
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TMB (Tumor Mutational Burden)
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TMB-H • PD-L1 underexpression • TMB-L • PD-L1-L
11ms
Frequent expression of CD45RO memory T cell marker as well as low to high expression of PD-1 and PD-L1 inhibitory molecules in seminoma and dysgerminoma. (PubMed, J Reprod Immunol)
The frequent infiltration of CD45RO, along with variable expression of PD-1 and PD-L1 on TILs and tumor cells, could impact the effectiveness of anti-tumor responses and immunotherapy.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1)
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PD-L1 overexpression • PD-L1 underexpression • PD-1 expression
11ms
The effects of anti-PD-L1 monoclonal antibody on the expression of angiogenesis and invasion-related genes. (PubMed, Turk J Biol)
The activation of angiogenesis and metastasis-related pathways by anti-PD-L1 treatment in PD-L1 high tumors might be a tumor-promoting mechanism. The decrease of VEGFA, TGFβ1 and EGFR upon anti-PD-L1 treatment in PD-L1 low tumor cells provides a rationale for the use of those antibodies in PD-L1 low tumors.
Journal • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • CDH1 (Cadherin 1) • TGFB1 (Transforming Growth Factor Beta 1)
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PD-L1 expression • PD-L1 overexpression • EGFR expression • PD-L1 underexpression • CDH1 expression • VEGFA expression • PD-L1-L
11ms
TLR9 activation induces immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in oral squamous cell carcinoma. (PubMed, Am J Physiol Cell Physiol)
Additionally, in vivo experiments further verified that TLR9 promoted tumour growth and immune escape by inhibiting PARP1. Collectively, TLR9 activation induced immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in OSCC, providing important insights for subsequent in-depth exploration of the mechanism of OSCC.
Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TLR9 (Toll Like Receptor 9)
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PD-L1 expression • PD-L1 overexpression • PD-L1 underexpression • TLR9 expression
12ms
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
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PD-L1 expression • PD-L1 underexpression • PD-L1 negative
12ms
PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 underexpression • PD-L1-L
12ms
PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 underexpression • PD-L1-L
12ms
PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 underexpression • PD-L1-L
1year
Combination of local radiotherapy and anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) therapy augments PD-L1 blockade-mediated anti-tumor effects in murine breast cancer model. (PubMed, Radiother Oncol)
The combination of local RT and an anti-GITR agonist significantly enhanced the anti-tumor immune responses induced by PD-L1 blockade. These results provide the preclinical rationale for the combination of therapy.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • TNFRSF8 (TNF Receptor Superfamily Member 8) • TNFA (Tumor Necrosis Factor-Alpha) • TNFRSF18 (TNF Receptor Superfamily Member 18)
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PD-L1 underexpression
1year
Novel Metrics of HER2 Heterogeneity in HER2-Positive and HER2-Low Breast Cancer via High Dimensional Multiplexed Immunofluorescence Spatial Profiling (SABCS 2023)
We present novel metrics of HER2 heterogeneity via HDmIF, which offer detailed characterization of the diversity of HER2 expression in a large, clinically-annotated cohort with long-term follow-up. Identification of a strong association between immunophenotype and RFS supports further investigation of the highly immune activated subsets of ER-/HER2+ breast cancer. Strong correspondence of HER2 IF and IHC and our HAIQu methodology offers a pathway to translation of HER2het metrics to clinical practice.
PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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HER-2 positive • HER-2 expression • PD-L1 underexpression • HR negative • ERBB3 expression • PD-1-L • PD-L1-L
1year
Immune Landscape in PD-L1-positive and TROP2-positive Triple-Negative Breast Cancer (SABCS 2023)
The recent approvals and data of pembrolizumab (anti-PD-1 inhibitor) in combination with chemotherapy in advanced-metastatic and early high-risk TNBC, and sacituzumab govitecan (an ADC that targets the tumor cell surface antigen TROP2 coupled with the irinotecan metabolite SN-38) in metastatic TNBC, has shed light on some of the immune and cancer signaling associated with TNBC. This preliminary analysis confirmed that only a limited number of early TNBC highly expressed PD-L1 and that a different immune suppressive landscape for PD-L1± and TROP2± tumors exists. In addition, our data suggest that early TNBC cases lacking PD-L1 might escape immune surveillance by virtue of the upregulation of key alternate signaling. Ongoing efforts investigating the expression of such markers on stroma/epithelial tumor components will help to clarify their biological, clinical, and potential therapeutic role in TNBC.
PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • IFNG (Interferon, gamma) • MUC1 (Mucin 1) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • STAT1 (Signal Transducer And Activator Of Transcription 1) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
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PD-L1 expression • PD-L1 overexpression • HER-2 expression • PD-L1 underexpression • TROP2 expression • VTCN1 underexpression • TROP2 positive • VTCN1 expression • PD-L1-L
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Keytruda (pembrolizumab) • irinotecan • Trodelvy (sacituzumab govitecan-hziy)
1year
Identifying new immune-related biomarkers in TNBC with a look at PD-L1 cell-autonomous role. (SABCS 2023)
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.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • NT5E (5'-Nucleotidase Ecto) • MIR320A (MicroRNA 320a) • MIR145 (MicroRNA 145) • MIR30E (MicroRNA 30e)
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PD-L1 expression • PD-L1 overexpression • PD-L1 underexpression • PD-L1 negative • CD73 expression • PD-1-L • PD-L1-L
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Imfinzi (durvalumab)
1year
Durvalumab + datopotamab deruxtecan in patients with PD-L1 positive advanced/metastatic triple-negative breast cancer: Arm 8 of the phase 1b/2, open label, platform BEGONIA study (SABCS 2023)
BEGONIA is an ongoing Simon 2-stage, multicenter, multi-arm platform study evaluating the safety and efficacy of durvalumab (D), an anti–PD-L1 monoclonal antibody, with or without paclitaxel, in combination with novel oncology therapies as first-line treatment for a/mTNBC (NCT03742102). TROP2 expression will be assessed by IHC. Enrollment is ongoing.
P1/2 data • Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
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PD-L1 expression • PD-L1 underexpression • TROP2 expression • PD-L1-L
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VENTANA PD-L1 (SP263) Assay
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Imfinzi (durvalumab) • paclitaxel • datopotamab deruxtecan (DS-1062a)
1year
Classic Hodgkin Lymphomas Display Neuronal-Glial Lineage Transdifferentiation (ASH 2023)
1N). Altogether, these single-cell multi-omics studies indicated that an epigenetically encoded NG program may cooperate with lymphoma driving mutations to drive the development of HL, paving novel avenues of therapy.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • CCR7 (Chemokine (C-C motif) receptor 7) • CCL2 (Chemokine (C-C motif) ligand 2) • CD79A (CD79a Molecule) • SOCS1 (Suppressor Of Cytokine Signaling 1) • CCL22 (C-C Motif Chemokine Ligand 22) • H1-4 (H1.4 Linker Histone, Cluster Member) • NRG2 (Neuregulin 2) • RACK1 (Receptor For Activated C Kinase 1)
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PD-L1 underexpression • CD19 expression
1year
Study of WM-A1-3389 in Participants With Advanced or Metastatic Solid Tumors and Non-Small Cell Lung Cancer (KEYNOTE-E90) (clinicaltrials.gov)
P1, N=54, Not yet recruiting, Wellmarker Bio | Trial completion date: Sep 2025 --> Feb 2026 | Initiation date: Aug 2023 --> Jan 2024 | Trial primary completion date: Sep 2025 --> Feb 2026
Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy • Metastases
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 underexpression • PD-L1-L
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Keytruda (pembrolizumab) • WM-A1-3389
1year
Development and Preclinical Evaluation of [Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 Expression. (PubMed, Pharmaceuticals (Basel))
Micro-PET/CT imaging of tumor-bearing mice further confirmed that, compared to &lsqb;F]FDG, &lsqb;Ga]BMSH can specifically identify tumors with varying levels of PD-L1 expression. Our findings suggest that the &lsqb;Ga]BMSH is a PD-L1 radioligand with ideal imaging properties, and its further application in the clinical screening of PD-L1 overexpressing tumors may improve ORR for immunotherapy.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 overexpression • PD-L1 underexpression • PD-L1-L
1year
PD-L1 Expression by RNA-Sequencing in Non-Small Cell Lung Cancer: Concordance with Immunohistochemistry and Associations with Pembrolizumab Treatment Outcomes. (PubMed, Cancers (Basel))
Conventional PD-L1 IHC testing has inherent limitations, making it an imperfect reference standard for evaluating novel testing technologies. RNA-seq offers an objective PD-L1 measure that could represent a complementary method to IHC to improve NSCLC patient selection for immunotherapy.
Journal • PD(L)-1 Biomarker • IO biomarker • Discordant
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PD-L1 (Programmed death ligand 1)
|
PD-L1 expression • PD-L1 underexpression • PD-L1 negative
|
Keytruda (pembrolizumab)
1year
PD-L1 on large extracellular vesicles is a predictive biomarker for therapy response in tissue PD-L1-low and -negative patients with non-small cell lung cancer (DGHO 2023)
Our data have identified PD-L1 + lEVs as a novel predictive and prognostic marker for immunotherapy in NSCLC that is superior to the standard-of-care measurement of tissue PD-L1 in selecting responders for immunotherapy.
Clinical • PD(L)-1 Biomarker • IO biomarker
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PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • SELP (Selectin P)
|
PD-L1 expression • PD-L1 underexpression • PD-L1-L
1year
Association between PD-L1 and Ki-67 expression and clinicopathologic features in NSCLC patients. (PubMed, Am J Transl Res)
The expression of PD-L1 and Ki-67 is related to some clinicopathologic features and inflammatory factors, which brings new sight for exploiting combination biomarkers and therapeutic strategies.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
|
PD-L1 expression • PD-L1 underexpression
1year
Programmed Death 1 (PD-1) Expression in Relapsing and Remitting Hodgkin Lymphoma as Prognostic Factor. (PubMed, Asian Pac J Cancer Prev)
PD-L1 expression assessment in HL patients is a valuable tool for prediction of the disease subtype, progression, stage, and treatment outcome. IHC method as an available, simple, rather cheap, and efficient tool could use for evaluation of PD-L1 expression and predicting the prognosis of HL disease, elsewhere.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1)
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PD-L1 overexpression • PD-L1 underexpression
1year
Prostate cancer cells synergistically defend against CD8 T cells by secreting exosomal PD-L1. (PubMed, Cancer Med)
In summary, tumor cells share PD-L1 synergistically against T cells through exosomes. Inhibition of exosome secretion or prevention of PD-L1 sorting into exosomes may improve the therapeutic response of prostate tumors to anti-PD-L1 therapy.
Journal
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1)
|
PD-L1 expression • PD-L1 underexpression • PD-L1-L
1year
Evaluation of programmed cell death ligand 1 expression in a contemporary cohort of penile squamous cell carcinoma and its correlation with clinicopathologic and survival parameters: A study of 134 patients. (PubMed, Am J Clin Pathol)
Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1-based immunotherapeutics in PC.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
|
PD-L1 expression • PD-L1 overexpression • PD-L1 underexpression • PD-L1 negative • CDKN2A negative • PD-L1-L
over1year
AN UNSUAL AND MASQUERADING CASE OF METASTATIC OR MULTIFOCAL PULMONARY ADENOCARCINOMA: CASE OF LOOKING BEYOND THE APPARENT (CHEST 2023)
We demonstrate a case of rapidly progressing multiple bilateral pulmonary nodules in short interval of 3 months that turned out to be lung adenocarcinoma.
Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 underexpression