The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker

By D. Jardim, A. Goodman, D. Gagliato, Razelle Kurzrock. Cancer Cell, 2020

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SUMMARY 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.

Subfields: Cancer Research, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/93fbc2efb0a7907ef932bbcb115639b5ca6bde30