The Challenges of Tumor Mutational Burden As an Immunotherapy Biomarker

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2020 Oct 30

PMID 33125859

Citations 525

Authors

Denis L Jardim

Aaron Goodman

Debora de Melo Gagliato

Razelle Kurzrock

Affiliations

Soon will be listed here.

Abstract

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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