ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Tumor Mutational Burden as a Predictor of Immunotherapy Response: Is More Always Better?
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 271 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
271 citing papers in PubMed, 4 syntheses or guidelines pooled it, 411 citations in OpenAlex.
- The risk of infection-related malignancies and tumor mutational burden in immunocompromised hosts: a systematic review and meta-analysis.BMC cancer · 2026Pooled it
- Research landscape, thematic evolution, and translational insights of immune checkpoint inhibitor-induced colitis: a bibliometric analysis (2006-2025).Frontiers in immunology · 2026Pooled it
- Real-world avelumab first-line maintenance in advanced urothelial carcinoma: systematic review and meta-analysis.Future oncology (London, England) · 2025Pooled it
- Applications of lung cancer organoids in precision medicine: from bench to bedside.Cell communication and signaling : CCS · 2023Pooled it
- Exploratory genomic stratification of benefit from first-line immunotherapy-based combination in advanced biliary tract cancer: a biomarker analysis of a randomized phase 2 trial.Frontiers in immunology · 2026Trial
- Multicenter phase II trial of ipilimumab and nivolumab in metastatic or unresectable perivascular epithelioid cell tumor (PEComa): a substudy ofJournal for immunotherapy of cancer · 2025Trial
- Influence of oncogenic drivers and signaling pathways on immune checkpoint inhibitor efficacy in NSCLC.Genes & diseases · 2027Review
- Laboratory diagnostics in personalised medicine - 36th Symposium of the Croatian society of medical biochemistry and laboratory medicine.Biochemia medica · 2026Review
- Review
- Endobronchial Intratumoral Immuno- and Gene Therapies in Lung Cancer: Mechanisms of Local Delivery, Systemic Immune Effects, and Global Feasibility.International journal of molecular sciences · 2026Review
- Gene mutant dosage is associated with prognosis and metastatic tropism in 60,000 clinical cancer samples.Nature genetics · 2026Article
- Loss-of-Function Mutations in SWI/SNF Complexes Associated With Active Tumour Immune Microenvironment Clinical Response to Immune Checkpoint Blockade.Journal of cellular and molecular medicine · 2026Article
- Rational design of anticancer multidrug nanosystems and their adaptation for glioblastoma treatment.Drug delivery and translational research · 2026Review
- Immune Regulation and the Role of Extracellular Vesicles in Non-Small Cell Lung Cancer: Biological Mechanisms and Therapeutic Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Pertussis toxin-induced lymphocytosis shifts the tumor microenvironment toward immune activation via CXCL9 signaling.Cancer immunology, immunotherapy : CII · 2026Article
- Whole genome sequencing in oesophageal adenocarcinoma unmasks potential precision therapies.BMC cancer · 2026Article
- Predicting of survival in metastatic melanoma patients under anti-PD-1 monotherapy using genomic mutation and copy number variation.Discover oncology · 2026Article
- New biological insights into osteosarcoma-lessons from single cell sequencing studies.Cancer metastasis reviews · 2026Review
- Investigation of the Prevalence of Associated Genetic Mutations (Co-Mutations) in Patients with Actionable Driver Mutations in Lung Cancer: A Retrospective Study.Diagnostics (Basel, Switzerland) · 2026Article
- Second Line Treatment Decision as Per Standard of Care or Foundation Medicine in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer.Cancer medicine · 2026Article
211 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Immune checkpoint inhibitors, including antibodies that block programmed cell death protein-1 (PD-1) and PD-L1, have transformed the management of many cancers. However, the majority of patients have primary or acquired resistance to these immunotherapies. There is a significant unmet need for predictive biomarkers that can reliably identify patients who derive a clinically meaningful response from PD-1/PD-L1 blockade. High tumor mutational burden (TMB-H) has shown promise as a biomarker in lung cancer, but the broad applicability of TMB-H as a biomarker of response across all solid tumors is unclear. The FDA has approved the PD-1 inhibitor, pembrolizumab, as a therapy for all solid tumors with TMB equal to or greater than 10 mutations/megabase as measured by the FoundationOne CDx assay. This approval was based on an exploratory analysis of the KEYNOTE-158 study, which was a single-arm, phase II multi-cohort study of pembrolizumab for select, previously treated advanced solid tumors. Here, we elucidate the caveats of using TMB as a biomarker with a universal threshold across all solid tumors. While we recognize the importance of this and other FDA pan-cancer approvals, several questions about TMB as a predictive biomarker remain unanswered. In this perspective, we discuss clinical trial evidence in this area. We review the relationship between TMB and the tumor immune microenvironment. We highlight the risks of extrapolating evidence from a limited number of tumor histologies to all solid tumors, and we propose avenues for future research.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.