The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker.
biomarker
cancer therapy
genetics
immunotherapy
mutattional load
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
08 02 2021
08 02 2021
Historique:
received:
06
04
2020
revised:
04
08
2020
accepted:
30
09
2020
pubmed:
31
10
2020
medline:
29
9
2021
entrez:
30
10
2020
Statut:
ppublish
Résumé
Tumor mutational burden (TMB) reflects cancer mutation quantity. Mutations are processed to neo-antigens and presented by major histocompatibility complex (MHC) proteins to T cells. To evade immune eradication, cancers exploit checkpoints that dampen T cell reactivity. Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by enabling T cell reactivation; however, response biomarkers are required, as most patients do not benefit. Higher TMB results in more neo-antigens, increasing chances for T cell recognition, and clinically correlates with better ICI outcomes. Nevertheless, TMB is an imperfect response biomarker. A composite predictor that also includes critical variables, such as MHC and T cell receptor repertoire, is needed.
Identifiants
pubmed: 33125859
pii: S1535-6108(20)30495-5
doi: 10.1016/j.ccell.2020.10.001
pmc: PMC7878292
mid: NIHMS1638412
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
154-173Subventions
Organisme : NCI NIH HHS
ID : P30 CA023100
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests D.L.J. receives speaker fees from Roche, Janssen, Astellas, MSD, Bristol-Myers Squibb, and Libbs, as well as consultant fees from Janssen, Bristol-Myers Squibb, and Libbs. A.G. receives consultant fees from EUSA Pharma Inc and Seattle Genetics. D.d.M.G. receives speaker fees from Roche, AstraZeneca, Pfizer, Lilly, Amgen, United Medical, and Libbs, as well as consultant fees from Libbs. R.K. receives research funding from Genentech, Merck Serono, Pfizer, Boehringer Ingelheim, TopAlliance, Takeda, Incyte, Debiopharm, Medimmune, Sequenom, Foundation Medicine, Konica Minolta, Grifols, Omniseq, and Guardant, as well as consultant and/or speaker fees, and/or is on the advisory board for X-Biotech, Neomed, Pfizer, Actuate Therapeutics, and Roche; has an equity interest in IDbyDNA and CureMatch, Inc.; serves on the board of CureMatch and CureMetrix; and is a co-founder of CureMatch.
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