The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker. Cancer Cell 2021 Feb 08;39(2):154-173
Date
10/31/2020Pubmed ID
33125859Pubmed Central ID
PMC7878292DOI
10.1016/j.ccell.2020.10.001Scopus ID
2-s2.0-85095988063 (requires institutional sign-in at Scopus site) 436 CitationsAbstract
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.
Author List
Jardim DL, Goodman A, de Melo Gagliato D, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Biomarkers, TumorHumans
Immunotherapy
Major Histocompatibility Complex
Mutation
Neoplasms
T-Lymphocytes