ArticleCancers2022
Interplay between Tumor Mutational Burden and Mutational Profile and Its Effect on Overall Survival: A Pilot Study of Metastatic Patients Treated with Immune Checkpoint Inhibitors.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Pan-cancer landscape of protein kinase D3: An integrative TCGA multi-omics analysis of clinical, molecular, and immunological roles.PloS one · 2026Article
- TMB as a predictive biomarker for ICI response in TNBC: current evidence and future directions for augmented anti-tumor responses.Clinical and experimental medicine · 2025Review
- Comprehensive analysis Neddylation-related genes identified UBB as a prognostic biomarker for clear cell renal cell carcinoma.Discover oncology · 2025Article
- Identifying predictors of overall survival among patients with TMB-low metastatic cancer treated with immune checkpoint inhibitors.The oncologist · 2025Article
- Advances in immunotherapy for bladder cancer and clinical practice of next-generation sequencing.Frontiers in immunology · 2025Review
- The role of CD8Heliyon · 2024Review
- Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance.Cancers · 2024Review
- The Role of Human Endogenous Retroviruses in Cancer Immunotherapy of the Post-COVID-19 World.Cancers · 2023Article
- A 20-gene mutation signature predicts the efficacy of immune checkpoint inhibitor therapy in advanced non-small cell lung cancer patients.BMC pulmonary medicine · 2023Article
- Biomarkers in the Era of Precision Oncology.Cancers · 2023Article
- Tumor Microenvironment and Metabolism: Role of the Mitochondrial Melatonergic Pathway in Determining Intercellular Interactions in a New Dynamic Homeostasis.International journal of molecular sciences · 2022Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Solid tumors harboring tumor mutational burden (TMB) ≥10 mutations per megabase (mut/Mb) received agnostic approval for pembrolizumab. This work aims to analyze the somatic mutational profile’s influence on the outcomes of patients with TMB-high tumors treated with immune checkpoint inhibitors (ICIs). Methods: This post-hoc analysis evaluated clinical and molecular features of patients with solid tumors treated with ICIs that could be either monoclonal antibody directed against programmed cell death protein-1 or monoclonal antibody directed against programmed cell death ligand 1 (anti-PD-1/anti-PD-L1), monoclonal antibody directed against cytotoxic T lymphocyte-associated antigen (anti-CTLA-4) or a combined treatment regimen including one anti-PD-1/anti-PD-L1 and one anti-CTLA-4 (ICIs combination). We performed OS analysis for TMB thresholds of ≥10, ≥20, and <10 mut/Mb. We assessed OS according to the mutational profile for a TMB ≥ 10 mut/Mb cutoff. For genes correlated with OS at the univariate assessment, we conducted a Cox multivariate analysis adjusted by median TMB, sex, age, microsatellite instability (MSI), and histology. Results: A total of 1661 patients were investigated; 488 with a TMB ≥10 mut/Mb (29.4%). The median OS was 42 months for TMB ≥10 or 20 mut/Mb, and 15 months for TMB <10 mut/Mb (p < 0.005). Among TMB ≥10 mut/Mb patients, mutations in E2F3 or STK11 correlated with worse OS, and mutations in NTRK3, PTPRD, RNF43, TENT5C, TET1, or ZFHX3 with better OS. These associations were confirmed with univariate and multivariate analyses (p < 0.05). Melanoma histology and TMB above the median endowed patients with better OS (p < 0.05), while MSI status, age, and gender did not have a statistically significant effect on OS. Conclusion: Combining TMB and mutation profiles in key cancer genes can better qualify patients for ICI treatment and predict their OS.
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