Checkpoint inhibitors and gastrointestinal immune-related adverse events

Curr Opin Oncol. 2016 Jul;28(4):264-8. doi: 10.1097/CCO.0000000000000292.

Abstract

Purpose of review: Recent development of checkpoint inhibitors is a challenge for oncologists. Indeed, it leads to specific immune adverse events, close to autoimmune disorders, which require a specific management. Colitis is one of the most frequent immune adverse events, in particular with anticytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy.

Recent findings: Severe colitis is frequent with immune checkpoint inhibitors and leads in a few cases to bowel perforation and death. This review focuses on specific pathogenic pathway and recent findings on risk factors and managements of colitis.

Summary: Anti-CTLA-4 antibodies are the most involved immune checkpoint inhibitors in colitis, and the combinations with anti-programmed death ligand 1 dramatically increase the rate of colitis. The early use of budesonide, and in some cases corticosteroids and/or infliximab should be recommended, as colitis is responsive to infliximab in almost all cases. Immune-related colitis shares some characteristics with inflammatory bowel disease but with little specificity. In particular, it has been recently showed that gut microbiota could interact with anti-CTLA-4 treatment to modulate efficacy but also to induce colitis. This opens the way for preventive or curative treatments capable of inducing modulation of the microbiota or fecal transplantation.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • CTLA-4 Antigen / antagonists & inhibitors*
  • CTLA-4 Antigen / immunology
  • Colitis / chemically induced
  • Colitis / immunology
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / immunology
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / immunology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • CTLA-4 Antigen
  • CTLA4 protein, human