ArticleGenome medicine2020
Burden of tumor mutations, neoepitopes, and other variants are weak predictors of cancer immunotherapy response and overall survival.
Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed.
- Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer.Journal for immunotherapy of cancer · 2021Trial
- Baseline and early functional immune response is associated with subsequent clinical outcomes of PD-1 inhibition therapy in metastatic melanoma patients.Journal for immunotherapy of cancer · 2021Trial
- E2F3 amplification primes bladder cancer cells for premature mitosis.Cancer gene therapy · 2026Article
- Predicting Immunotherapy Outcomes in NSCLC Using RNA and Pathology from Multicenter Clinical Trials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- The role of neoantigens and tumor mutational burden in cancer immunotherapy: advances, mechanisms, and perspectives.Journal of hematology & oncology · 2025Review
- Identification and validation of prognostic genes associated with mitochondrial nuclear genes in gastric cancer.Clinical and experimental medicine · 2025Article
- Detecting known neoepitopes, gene fusions, transposable elements, and circular RNAs in cell-free RNA.Bioinformatics (Oxford, England) · 2025Article
- Different NGS identification methods of somatic mutation sites in solid tumors impact TMB results.BMC cancer · 2025Article
- The promise of PD1/PDL1 targeted immunotherapy in locally advanced cervical cancer: a game-changer for patients outcome?Frontiers in immunology · 2025Review
- Article
- Identifying Strong Neoantigen MHC-I/II Binding Candidates for Targeted Immunotherapy with SINE.International journal of molecular sciences · 2024Article
- SpliceMutr Enables Pan-Cancer Analysis of Splicing-Derived Neoantigen Burden in Tumors.Cancer research communications · 2024Article
- Early kinetics of C-reactive protein as prognosticator for survival in a real-world cohort of patients with metastatic renal cell cancer under first-line therapy with immune checkpoint inhibitors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Intragenic Rearrangement Burden Associates with Immune Cell Infiltration and Response to Immune Checkpoint Blockade in Cancer.Cancer immunology research · 2024Article
- TMBocelot: an omnibus statistical control model optimizing the TMB thresholds with systematic measurement errors.Frontiers in immunology · 2024Article
- Challenges and Future Directions in the Management of Tumor Mutational Burden-High (TMB-H) Advanced Solid Malignancies.Cancers · 2023Review
- Multiple instance learning to predict immune checkpoint blockade efficacy using neoantigen candidates.iScience · 2023Article
- OutSplice: A Novel Tool for the Identification of Tumor-Specific Alternative Splicing Events.BioMedInformatics · 2023Article
- Biomarkers for Immune Checkpoint Inhibitors in Renal Cell Carcinoma.Journal of clinical medicine · 2023Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
backgroundTumor mutational burden (TMB; the quantity of aberrant nucleotide sequences a given tumor may harbor) has been associated with response to immune checkpoint inhibitor therapy and is gaining broad acceptance as a result. However, TMB harbors intrinsic variability across cancer types, and its assessment and interpretation are poorly standardized.
methodsUsing a standardized approach, we quantify the robustness of TMB as a metric and its potential as a predictor of immunotherapy response and survival among a diverse cohort of cancer patients. We also explore the additive predictive potential of RNA-derived variants and neoepitope burden, incorporating several novel metrics of immunogenic potential.
resultsWe find that TMB is a partial predictor of immunotherapy response in melanoma and non-small cell lung cancer, but not renal cell carcinoma. We find that TMB is predictive of overall survival in melanoma patients receiving immunotherapy, but not in an immunotherapy-naive population. We also find that it is an unstable metric with potentially problematic repercussions for clinical cohort classification. We finally note minimal additional predictive benefit to assessing neoepitope burden or its bulk derivatives, including RNA-derived sources of neoepitopes.
conclusionsWe find sufficient cause to suggest that the predictive clinical value of TMB should not be overstated or oversimplified. While it is readily quantified, TMB is at best a limited surrogate biomarker of immunotherapy response. The data do not support isolated use of TMB in renal cell carcinoma.
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