Toxicity in the era of immune checkpoint inhibitor therapy

Front Immunol. 2024 Aug 23:15:1447021. doi: 10.3389/fimmu.2024.1447021. eCollection 2024.

Abstract

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory immune checkpoint molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success and have become the standard of care for many cancers, they are often accompanied by off-target inflammation that can occur in any organ system. These immune related adverse events (irAEs) often require steroid use and/or cessation of ICI therapy, which can both lead to cancer progression. Although irAEs are common, the detailed molecular and immune mechanisms underlying their development are still elusive. To further our understanding of irAEs and develop effective treatment options, there is pressing need for preclinical models recapitulating the clinical settings. In this review, we describe current preclinical models and immune implications of ICI-induced skin toxicities, colitis, neurological and endocrine toxicities, pneumonitis, arthritis, and myocarditis along with their management.

Keywords: immune checkpoint; immune related adverse events; immunotherapy; preclinical model; treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / immunology
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Immune Checkpoint Inhibitors* / adverse effects
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy / adverse effects
  • Immunotherapy / methods
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology

Substances

  • Immune Checkpoint Inhibitors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by NIH R01 grants (R.N.: R01HL141966, R01HL143520, and R01CA284684) and NIH Loan Repayment Program (LRP) grant (A.E.A: 1L30TR005243-01). SA is supported by a CPRIT Research Training Award RP210028.