Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

Mol Cancer. 2018 Aug 23;17(1):129. doi: 10.1186/s12943-018-0864-3.

Abstract

Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) is a negative modulatory signaling pathway for activation of T cell. It is acknowledged that PD-1/PD-L1 axis plays a crucial role in the progression of tumor by altering status of immune surveillance. As one of the most promising immune therapy strategies, PD-1/PD-L1 inhibitor is a breakthrough for the therapy of some refractory tumors. However, response rate of PD-1/PD-L1 inhibitors in overall patients is unsatisfactory, which limits the application in clinical practice. Therefore, biomarkers which could effectively predict the efficacy of PD-1/PD-L1 inhibitors are crucial for patient selection. Biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, density of tumor infiltrating lymphocyte (TIL), tumor mutational burden, and mismatch-repair (MMR) deficiency, have been noticed to associate with treatment effect of anti-PD-1/anti-PD-L1 therapy. Furthermore, gut microbiota, circulating biomarkers, and patient previous history have been found as valuable predictors as well. Therefore establishing a comprehensive assessment framework involving multiple biomarkers would be meaningful to interrogate tumor immune landscape and select sensitive patients.

Keywords: Gut microbiota; Microsatellite instability; PD-1/PD-L1 inhibitors; Peripheral biomarker; Predictive biomarkers; Tumor mutational burden.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism
  • Humans
  • Immunotherapy / methods
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Mutation*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / metabolism
  • Treatment Outcome
  • Tumor Microenvironment

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor