{"entity":{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","aka":[],"tldr":"How many mutations a tumour has. More mutations mean more targets for the immune system.","summary":"Tumour mutational burden (TMB) counts how many mutations a tumour carries, expressed as mutations per megabase from panel or exome sequencing, on the logic that more mutations mean more targets for the immune system. A TMB of 10 mutations per megabase or higher is a tumour-agnostic indication for Pembrolizumab, established in KEYNOTE-158. It is an imperfect predictor and varies from panel to panel, which is why the idea of a single calibrated TMB across all sequencing panels exists and why the term features in the bottleneck on unvalidated biomarkers. TMB is linked to Comprehensive genomic profiling and Immune checkpoint inhibitors, to the Antigen presentation & immune editing pathway, and to Aurélien Marabelle, Ramaswamy Govindan and Timothy A. Chan.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tumor_mutational_burden","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_mutational_burden"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-rizvi-mutational-landscape-pd1-science-2015","paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018","paper-ricciuti-tmb-pd-l1-levels-jama-oncol-2022","paper-keynote-042-tmb-mutations-ann-oncol-2023","paper-keynote-189-407-tmb-jtocrr-2023"],"journals":[],"dependsOn":[],"notes":["Lung cancer is where tumour mutational burden was discovered as a predictor of checkpoint benefit (Rizvi 2015) and where it failed as a selector. The biology holds: burden tracks outcome within every PD-L1 stratum in 1,552 patients and is independent of PD-L1 (Rizvi 2018, Ricciuti 2022). The measurement does not: three units are in use (per megabase on a panel, per exome on sequencing, a plasma score), the best data-derived threshold was more than 19 per megabase rather than the licensed 10, and the association vanishes entirely once chemotherapy is added to the checkpoint inhibitor (Garassino 2023). It selects for single-agent immunotherapy only (Mok 2023)."],"category":"Biomarkers"},"route":"/terms/tmb/","neighbours":{"cancer":[{"id":"advanced-adrenocortical-carcinoma","kind":"cancer","name":"Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable)","route":"/cancers/advanced-adrenocortical-carcinoma/"},{"id":"advanced-cutaneous-scc","kind":"cancer","name":"Advanced cutaneous squamous cell carcinoma","route":"/cancers/advanced-cutaneous-scc/"},{"id":"basal-cell-carcinoma","kind":"cancer","name":"Basal cell carcinoma","route":"/cancers/basal-cell-carcinoma/"},{"id":"cancer-of-unknown-primary","kind":"cancer","name":"Cancer of unknown primary (CUP)","route":"/cancers/cancer-of-unknown-primary/"},{"id":"cup-unfavourable","kind":"cancer","name":"Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma)","route":"/cancers/cup-unfavourable/"},{"id":"colorectal","kind":"cancer","name":"Colorectal 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