title: Checkpoint inhibitors and gastrointestinal immune-related adverse events.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris Descartes University, Paris, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Pernot
authors.forename: Toulsie
authors.initials: T
authors.lastname: Ramtohul
authors.forename: Julien
authors.initials: J
authors.lastname: Taieb
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000276:immunology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human