Evolving insights into the mechanisms of toxicity associated with immune checkpoint inhibitor therapy

Br J Clin Pharmacol. 2020 Sep;86(9):1778-1789. doi: 10.1111/bcp.14433. Epub 2020 Jul 17.

Abstract

Immune checkpoint inhibitors have emerged as a revolutionary treatment option for patients with various types of malignancy. Although these agents afford a significant improvement in outcomes for melanoma and other previously untreatable malignancies, their novel mechanism of action may predispose patients to immune-related adverse effects (irAEs). In the tumour neoantigen environment, these irAEs are due to the activation of the immune system by the blockade of suppressive checkpoints, leading to increases in T-cell activation and proliferation. IrAEs have been reported in almost any organ and at any point in time, even months to years after discontinuation of therapy. Certain populations with distinct physiological changes, genetic risk factors, and specific antigen exposures may be more highly predisposed to develop irAEs. This review discusses the incidence and mechanisms of irAEs and the relationship between host factors and irAE occurrence.

Keywords: cytotoxic T-lymphocyte antigen-4, immune checkpoint inhibitors, immune-related adverse effects, immunotherapy, programmed cell death 1, programmed cell death ligand 1.

Publication types

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

MeSH terms

  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Immune Checkpoint Inhibitors*
  • Incidence
  • Melanoma* / drug therapy
  • Neoplasms* / drug therapy
  • Programmed Cell Death 1 Receptor / therapeutic use

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor