Next generation predictive biomarkers for immune checkpoint inhibition

Cancer Metastasis Rev. 2017 Mar;36(1):179-190. doi: 10.1007/s10555-016-9652-y.


With the advent of targeted therapies, there has been a revolution in the treatment of cancer across multiple histologies. Immune checkpoint blockade has made it possible to take advantage of receptor-ligand interactions between immune and tumor cells in a wide spectrum of malignancies. Toxicity in healthy tissue, however, can limit our use of these agents. Immune checkpoint blockade has been approved in advanced melanoma, renal cell cancer, non-small cell lung cancer, relapsed refractory Hodgkin's lymphoma, and urothelial cancer. Though FDA-approved indications for use of some of these novel agents depend on current protein-based programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) assays, detection methods come with several caveats. Additional predictive tools must be interrogated to discern responders from non-responders. Some of these include measurement of microsatellite instability, PD-L1 amplification, cluster of differentiation 8 (CD8) infiltrate density, and tumor mutational burden. This review serves to synthesize biomarker detection at the DNA, RNA, and protein level to more accurately forecast benefit from these novel agents.

Keywords: Checkpoint inhibitor; Immunooncology; Neoantigen presentation; Predictive biomarker; Tumor microenvironment; Tumor mutational burden.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / antagonists & inhibitors
  • Biomarkers, Tumor / immunology*
  • CTLA-4 Antigen / antagonists & inhibitors
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors


  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor