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BIOMARKER:

PD-L1 negative + TMB-L

i
Other names: TMB | Tumor Mutational Burden, 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:
2ms
Correlation of clinical, genetic and transcriptomic traits with PD-L1 positivity in TNBC patients (ESMO-IO 2024)
Most DEGs were involved in the neuroactive ligand-receptor interactions, calcium, cAMP and cell adhesion signalling pathways. Immune, chemokine and JAK-STAT signalling pathways were positively enriched in PD-L1-high tumours.Conclusions This integrative analysis of clinical, genetic, transcriptomic and immunohistochemical data revealed differences in mutational signatures and gene expression patterns between PD-L1-high and -low TNBC tumours.
Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • JAK2 (Janus kinase 2) • IFNG (Interferon, gamma) • STAT1 (Signal Transducer And Activator Of Transcription 1)
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PD-L1 expression • TP53 mutation • BRCA1 mutation • PIK3CA mutation • PTEN mutation • TMB-L • PIK3CA mutation + PTEN mutation • PD-L1 negative + TMB-L
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PD-L1 IHC 22C3 pharmDx
5ms
TCR Metrics as Predictive Biomarkers of Response and Survival after Perioperative Chemoimmunotherapy. NADIM & NADIM II Trials (IASLC-WCLC 2024)
Similar results for biomarkers were observed in NADIM and NADIM II ChIO cohorts analyzed separately, and were not predictive of patients’ outcomes when analyzed in posttreatment samples or in chemotherapy treated patients. Conclusions : Baseline TCR metrics, particularly convergence, evenness, and TOP1% CS, demonstrate robust predictive value for CPR and survival in locally-advanced NSCLC patients undergoing perioperative nivolumab plus chemotherapy, warranting further investigation in larger cohorts.
Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
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PD-L1 negative • TMB-L • PD-L1 negative + TMB-L
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Oncomine™ TCR Beta-SR Assay
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Opdivo (nivolumab)
5ms
TCR Metrics as Predictive Biomarkers of Response and Survival after Perioperative Chemoimmunotherapy. NADIM & NADIM II Trials (IASLC-WCLC 2024)
Baseline TCR metrics, particularly convergence, evenness, and TOP1% CS, demonstrate robust predictive value for CPR and survival in locally-advanced NSCLC patients undergoing perioperative nivolumab plus chemotherapy, warranting further investigation in larger cohorts.
Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
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PD-L1 negative • TMB-L • PD-L1 negative + TMB-L
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Oncomine™ TCR Beta-SR Assay
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Opdivo (nivolumab)
9ms
Lifileucel, an Autologous Tumor-infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors. (PubMed, Cancer Discov)
In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell therapy, in patients with metastatic non-small cell lung cancer (mNSCLC) who had received prior immunotherapy and progressed on their most recent therapy. Two patients died of treatment-emergent adverse events: cardiac failure and multiple organ failure. Lifileucel is a potential treatment option for patients with mNSCLC refractory to prior therapy.
Clinical • Journal • Checkpoint inhibition • Tumor mutational burden • Tumor-infiltrating lymphocyte • PD(L)-1 Biomarker • IO biomarker • Metastases
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TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11)
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STK11 mutation • PD-L1 negative • TMB-L • PD-L1 negative + TMB-L
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Amtagvi (lifileucel) • LN-145
over1year
Association of Molecular Profiles and Mutational Status With Distinct Histological Lung Adenocarcinoma Subtypes. An Analysis of the LACE-Bio Data. (PubMed, Clin Lung Cancer)
High TMB has a prognostic role in resectable lung ADC. The high TMB group had a poor outcome with AC, suggesting that this group may be better served with immune checkpoint therapy.
Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
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TMB-H • PD-L1 negative • TMB-L • PD-L1 negative + TMB-L
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cisplatin • Undisclosed CISH inactivated TIL
over1year
Role of immune checkpoint inhibitors in PDL1-negative, low TMB, stable MSI metastatic solid tumours: Single centre study. (ASCO 2023)
Regardless of the presence of PDL1 expression, high TMB, or MSI, adding immune checkpoint inhibitors to the treatment regimen for metastatic head and neck malignancies and lung tumours that lack driver mutations is obviously advantageous. On the other hand, immunotherapy had no effect on gastrointestinal, gynaecological, or urothelial tumours. To validate these findings, more research with several centres and a sizable sample size is necessary.
Checkpoint inhibition • Clinical • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • BRCA (Breast cancer early onset)
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PD-L1 expression • TMB-H • PD-L1 overexpression • PD-L1 negative • TMB-L • BRCA mutation • PD-L1 negative + TMB-L
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PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
over1year
Stimulator of interferon gene (STING) expression as a biomarker for overall survival in PDL1-negative, TMB-low non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). (ASCO 2023)
To our knowledge this is the largest real-world dataset indicating that enrichment of both the STING gene, and gene signatures associated with the STING pathway represent valuable transcriptomic biomarkers to stratify pts with PDL1-negative and TMB-Low NSCLC who benefit more from IO therapies. Conversely, novel IO combination strategies need to be employed in STING-low tumors to enhance outcomes. >
Checkpoint inhibition • Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • CD8 (cluster of differentiation 8) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • STING (stimulator of interferon response cGAMP interactor 1) • CD80 (CD80 Molecule)
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TP53 mutation • STK11 mutation • PD-L1 negative • TMB-L • PD-L1 negative + TMB-L • PD-L1 negative + TMB-L + STING overexpression
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PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
2years
Predictors of Survival to Immunotherapy and Chemoimmunotherapy in Non-Small Cell Lung Cancer: A Meta-Analysis. (PubMed, J Natl Cancer Inst)
these findings suggest some clinicopathological and molecular features that, added to PD-L1 expression, could help in the selection of the most appropriate first-line IO-based treatment for advanced NSCLC patients.
Clinical • Retrospective data • Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
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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 negative • TMB-L • PD-L1 negative + TMB-L
over2years
Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
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PD-L1 negative • TMB-L • PD-L1 negative + TMB-L
over2years
The inflamed immune phenotype (IIP): A clinically actionable artificial intelligence (AI)-based biomarker predictive of immune checkpoint inhibitor (ICI) outcomes across >16 primary tumor types. (ASCO 2022)
The IIP, as evaluated by Lunit SCOPE IO, may represent a practical, clinically-actionable biomarker predictive of favorable ICI treatment outcomes across diverse cancer patient populations, including those with PD-L1 negative, MSS/TMB-low tumors, in whom predictive biomarkers are urgently needed.
Checkpoint inhibition • Clinical • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
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TMB-H • MSI-H/dMMR • PD-L1 negative • TMB-L • PD-L1 negative + TMB-L
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PD-L1 IHC 22C3 pharmDx • Lunit SCOPE IO
over3years
Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study. (PubMed, NPJ Breast Cancer)
High pretreatment levels of plasma immunosuppressive cytokines, chemokines, and immune checkpoint molecules were associated with rapid progression. Although this study did not meet its primary endpoint, immunostaining, genomic, and proteomic studies indicated a high degree of tumor immunosuppression in this mTNBC cohort.
P2 data • Journal • Combination therapy • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
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PD-L1 expression • PD-L1 negative • TMB-L • PD-L1 negative + TMB-L
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Opdivo (nivolumab) • Cabometyx (cabozantinib tablet)
almost4years
[VIRTUAL] An effective treatment for recurrent and inoperable anaplastic thyroid carcinoma using sintilimab and anlotinib: A case report (AACR 2021)
This case showed relatively good prognosis after using anti-angiogenic agent, anlotinib, and immunotherapeutic drug, sintilimab, suggesting a new direction in treating recurrent and inoperable ATC patients, and also providing a new way for cancer patients with PD-L1 negative/TMB-low.
Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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TP53 mutation • PD-L1 negative • TMB-L • HRAS mutation • PD-L1 negative + TMB-L
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Focus V (anlotinib) • Tyvyt (sintilimab)