title: Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora?
abstract: Checkpoint inhibitors blocking CTLA-4 (ipilimumab) and PD-1 (nivolumab, pembrolizumab) have transfigured our cancer treatment paradigm. However, these drugs can induce immune-related adverse events that share clinical and pathological characteristics with immune-mediated diseases. One of the most severe immune-related adverse event observed with anti-CTLA-4 is an enterocolitis that mirrors naturally occurring inflammatory bowel disease. This paper reviews the clinical, immunological, and microbiota data associated with the immune-related enterocolitis induced by the cancer immunotherapy blocking CTLA-4, ipilimumab. A parallel analysis of the mechanisms underlying inflammatory bowel diseases on the one hand, and anti-CTLA-4-induced colitis on the other hand, stresses the crucial role of the gut microbiota and of resident Tregin the genesis of both iatrogenic and spontaneous inflammatory bowel diseases.
authors.affiliation: Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France.|Université Paris-Sud, Faculté de Médecine, Le Kremlin Bicêtre, F-94276, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Carbonnel
authors.affiliation: Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France.|Université Paris-Sud, Faculté de Médecine, Le Kremlin Bicêtre, F-94276, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Soularue
authors.affiliation: Gustave Roussy, Laboratoire d'Immunomonitoring en Oncologie, and CNRS-UMS 3655 and INSERM-US23, Villejuif, F-94805, France.
authors.forename: Clélia
authors.initials: C
authors.lastname: Coutzac
authors.affiliation: Gustave Roussy, Laboratoire d'Immunomonitoring en Oncologie, and CNRS-UMS 3655 and INSERM-US23, Villejuif, F-94805, France.|Université Paris-Sud, Faculté de pharmacie, Chatenay-Malabry, Châtenay-Malabry, F-92296, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
authors.affiliation: Gustave Roussy, Département de Médecine, Service de Dermatologie, et Université Paris-Sud Villejuif, Villejuif, F-94805, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Mateus
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lepage
authors.affiliation: Gustave Roussy, Département de Médecine, Service de Dermatologie, et Université Paris-Sud Villejuif, Villejuif, F-94805, France. caroline.robert@gustaveroussy.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D003092:Colitis / Q000209:etiology; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D000074324:Ipilimumab; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D000074324:Ipilimumab