Tumor mutational burden for the prediction of PD-(L)1 blockade efficacy in cancer: challenges and opportunities

Ann Oncol. 2024 Jun;35(6):508-522. doi: 10.1016/j.annonc.2024.03.007. Epub 2024 Mar 26.

Abstract

Tumor mutational burden (TMB) is a biomarker that measures the number of somatic mutations in a tumor's genome. TMB has emerged as a predictor of response to immune checkpoint inhibitors (ICIs) in various cancer types, and several studies have shown that patients with high TMB have better outcomes when treated with programmed death-ligand 1-based therapies. Recently, the Food and Drug Administration has approved TMB as a companion diagnostic for the use of pembrolizumab in solid tumors. However, despite its potential, the use of TMB as a biomarker for immunotherapy efficacy is limited by several factors. Here we review the limitations of TMB in predicting immunotherapy outcomes in patients with cancer and discuss potential strategies to optimize its use in the clinic.

Keywords: PD-(L)1 blockade; TMB; biomarkers; neoantigens.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • B7-H1 Antigen* / antagonists & inhibitors
  • B7-H1 Antigen* / genetics
  • Biomarkers, Tumor* / genetics
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy / methods
  • Mutation*
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics

Substances

  • Immune Checkpoint Inhibitors
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Antibodies, Monoclonal, Humanized