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The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker.

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.

SUBMITTER: Jardim DL

PROVIDER: S-EPMC7878292 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker.

Jardim Denis L DL Goodman Aaron A de Melo Gagliato Debora D Kurzrock Razelle R

Cancer cell 20201029 2

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 ...[more]

PMID: 33125859

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