TMB: a promising immune-response biomarker, and potential spearhead in advancing targeted therapy trials

Cancer Gene Ther. 2020 Dec;27(12):841-853. doi: 10.1038/s41417-020-0174-y. Epub 2020 Apr 28.


Immune checkpoint inhibition (ICI) has revolutionized cancer treatment, and produced durable responses in many cancer types. However, there remains a subset of patients that do not respond despite their tumors exhibiting PD-L1 expression, which highlights the need for additional biomarkers relevant to response. Here, we review checkpoint inhibitor signal pathways, resistance and sensitivity mechanisms, as well as response rates. We also investigate the correlation and response to ICI with BRCA1/2 mutation status and homologous recombination deficient tumors. Collectively we show that the use of tumor mutational burden may be effective as an emerging biomarker.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / immunology*
  • Drug Resistance, Neoplasm
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunotherapy / methods*
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Tumor Burden


  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors