Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy

Cancer Treat Rev. 2015 Dec;41(10):868-76. doi: 10.1016/j.ctrv.2015.11.001. Epub 2015 Nov 10.

Abstract

Checkpoint blockades turn on a new paradigm shift in immunotherapy for cancer. Remarkable clinical efficacy, durable response and low toxicity of programmed death 1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint blockades have been observed in various malignancies. However, a lot of cancer patients failed to respond to the PD-1/PD-L1 checkpoint blockades. It is crucial to identify a biomarker to predict the response to checkpoint blockades. The overexpression of PD-L1 is an important and widely-explored predictive biomarker for the response to PD-1/PD-L1 antibodies. However PD-L1 staining cannot be used to accurately select patients for PD-1/PD-L1 pathway blockade due to the low prediction accuracy and dynamic changes. Tumor-infiltrating immune cells and molecules in the tumor microenvironment, or along with PD-L1 expression, may be important in predicting clinical benefits of PD-1/PD-L1 checkpoint blockades. Gene analysis has proven to be new approach for judging the potential clinical benefit of immune checkpoint inhibitors, such as mutational landscape and mismatch-repair deficiency. Further preclinical and clinical studies are necessary to carry out before its application in clinical practice. Challenges should be overcome to identify patients accurately who will benefit from PD-1/PD-L1 checkpoint blockades. In this review, we focus on the predictive biomarkers for checkpoint blockades of PD-1/PD-L1 pathway.

Keywords: Biomarkers; Immunotherapy; PD-1; PD-L1; Response.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Cell Cycle Checkpoints*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunotherapy
  • Ipilimumab
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Nivolumab
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / metabolism*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • Immunologic Factors
  • Ipilimumab
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • atezolizumab
  • pembrolizumab