Progress and challenges of predictive biomarkers of anti PD-1/PD-L1 immunotherapy: A systematic review

Cancer Lett. 2018 Feb 1:414:166-173. doi: 10.1016/j.canlet.2017.11.014. Epub 2017 Nov 16.

Abstract

Despite the marked success of applications of PD-1/PD-L1 checkpoint blockades in clinical, the efficacy and responsiveness of these agents varies greatly among different tumor types and across individual patients. Therefore, establishment of predictive biomarkers for checkpoint blockades is of the most importance to maximize the therapeutic benefits. In this review, we discuss the current progress and challenges of developing predictive biomarkers of immunotherapy responsiveness, aiming to provide some directions for future studies. PD-L1 expression is a logical biomarker for the prediction of response to anti-PD-(L)1 immunotherapies. However, the predictive values of PD-L1 expressions for immunotherapy are currently debating and challenging. Multiplex detecting methods and combined biomarkers may provide new strategies. For example, tumor mutation and neoantigens burden, some oncogene mutations, like EGFR, ALK, KRAS and STK11. In addition, with development of new probes and tracers, immuno-PET provide a new, non-invasive and quantitative strategy to monitor treatment response. As current evidence of those potential predictors, a consensus and standardization is needed to establish to widely applied in future studies. Multiplex detecting methods and combined biomarkers may provide new strategies.

Keywords: Biomarker; Immune-checkpoint; Immunotherapy; Predictive.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / antagonists & inhibitors*
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism
  • Humans
  • Immunotherapy / methods
  • Immunotherapy / trends
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Nivolumab
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • atezolizumab
  • pembrolizumab