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Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora?

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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 Treg in the genesis of both iatrogenic and spontaneous inflammatory bowel diseases.

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    Authors and Affiliations

    1. Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France

      Franck Carbonnel & Emilie Soularue

    2. Université Paris-Sud, Faculté de Médecine, Le Kremlin Bicêtre, F-94276, France

      Franck Carbonnel & Emilie Soularue

    3. Gustave Roussy, Laboratoire d’Immunomonitoring en Oncologie, and CNRS-UMS 3655 and INSERM-US23, Villejuif, F-94805, France

      Clélia Coutzac & Nathalie Chaput

    4. Université Paris-Sud, Faculté de pharmacie, Chatenay-Malabry, Châtenay-Malabry, F-92296, France

      Nathalie Chaput

    5. Gustave Roussy, Département de Médecine, Service de Dermatologie, et Université Paris-Sud Villejuif, Villejuif, F-94805, France

      Christine Mateus & Caroline Robert

    6. Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France

      Patricia Lepage

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    1. Franck Carbonnel
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    Correspondence to Caroline Robert.

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    This article is a contribution to the special issue on Cancer and Autoimmunity - Guest Editor: Mads Hald Andersen

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    Carbonnel, F., Soularue, E., Coutzac, C. et al. Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora?. Semin Immunopathol 39, 327–331 (2017). https://doi.org/10.1007/s00281-016-0613-x

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