Genomic correlates of response to immune checkpoint blockade

Nat Med. 2019 Mar;25(3):389-402. doi: 10.1038/s41591-019-0382-x. Epub 2019 Mar 6.


Despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Understanding genomic correlates of response and resistance to checkpoint blockade may enhance benefits for patients with cancer by elucidating biomarkers for patient stratification and resistance mechanisms for therapeutic targeting. Here we review emerging genomic markers of checkpoint blockade response, including those related to neoantigens, antigen presentation, DNA repair, and oncogenic pathways. Compelling evidence also points to a role for T cell functionality, checkpoint regulators, chromatin modifiers, and copy-number alterations in mediating selective response to immune checkpoint blockade. Ultimately, efforts to contextualize genomic correlates of response into the larger understanding of tumor immune biology will build a foundation for the development of novel biomarkers and therapies to overcome resistance to checkpoint blockade.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigen Presentation / genetics*
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / immunology
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology
  • Carcinogenesis / genetics
  • Chromatin Assembly and Disassembly / genetics
  • DNA Copy Number Variations / genetics
  • DNA Repair / genetics*
  • Drug Resistance, Neoplasm / genetics
  • Genome / genetics*
  • Humans
  • Mutation
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Signal Transduction
  • T-Lymphocytes / immunology*


  • Antigens, Neoplasm
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor