Mechanisms of Resistance to PD-1 and PD-L1 Blockade

Cancer J. Jan/Feb 2018;24(1):47-53. doi: 10.1097/PPO.0000000000000303.

Abstract

Cancer immunotherapy utilizing blockade of the PD-1/PD-L1 checkpoint has revolutionized the treatment of a wide variety of malignancies, leading to durable therapeutic responses not typically seen with traditional cytotoxic anticancer agents. However, these therapies are ineffective in a significant percentage of patients, and some initial responders eventually develop resistance to these therapies with relapsed disease. The mechanisms leading to both primary and acquired resistance to PD-1/PD-L1 inhibition are varied and can be both multifactorial and overlapping in an individual patient. As the mechanisms of resistance to PD-1/PD-L1 blockade continue to be further characterized, new strategies are being developed to prevent or reverse resistance to therapy, leading to improved patient outcomes.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors*
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Immunotherapy / methods
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor