Tumor mutational burden (TMB) has received significant attention within ongoing pursuits of biomarkers of response to immune checkpoint inhibitors, and notably received FDA approval as a companion diagnostic biomarker for pembrolizumab. Here, four experts discuss the utility, challenges, and open questions surrounding TMB in the context of cancer immunotherapy.
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V.A. receives research funding (paid to Johns Hopkins University) from AstraZeneca and has received research funding (paid to Johns Hopkins University) from Bristol Myers Squibb in the past 5 years. A.B. has received grants/research support from Neophore, AstraZeneca, and Boehringer, as well as honoraria or consultation fees from Illumina, Guardant Health, and Inivata. A.B. is a stock shareholder in Neophore and has served on scientific advisory boards for Inivata, Neophore, and Roche/Genentech Global CRC Advisory Board. T.A.C. is a co-founder of Gritstone Oncology and holds equity. T.A.C. holds equity in NysnoBio. T.A.C. acknowledges grant funding from Bristol Myers Squibb, AstraZeneca, Illumina, Pfizer, InterVenn, An2H, and Eisai. T.A.C. has served as an advisor for Bristol-Myers, MedImmune, Squibb, Illumina, Eisai, AstraZeneca, and An2H. T.A.C. is an inventor on intellectual property held by MSKCC on using tumor mutation burden to predict immunotherapy response, with pending patent (62/569,053), which has been licensed to PGDx. S.T. is funded by Cancer Research UK (grant reference number A29911); the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC10988), the UK Medical Research Council (FC10988), and the Wellcome Trust (FC10988); the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (grant reference number A2204), Ventana Medical Systems Inc (grant reference numbers 10467 and 10530), the National Institute of Health ((U01 CA247439) and Melanoma Research Alliance (award ref. no 686061). S.T. has received speaking fees from Roche, AstraZeneca, Novartis and Ipsen. S.T. has the following patent filed: Indel mutations as a therapeutic target and predictive biomarker (PCTGB2018/051892).
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Anagnostou, V., Bardelli, A., Chan, T.A. et al. The status of tumor mutational burden and immunotherapy. Nat Cancer 3, 652–656 (2022). https://doi.org/10.1038/s43018-022-00382-1
Nature Cancer (2022)