The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker.

Cancer Cell

Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA, USA. Electronic address:

Published: February 2021

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878292PMC
http://dx.doi.org/10.1016/j.ccell.2020.10.001DOI Listing

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