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Recent advances in basic science
Enterocolitis due to immune checkpoint inhibitors: a systematic review
  1. Emilie Soularue1,2,
  2. Patricia Lepage3,
  3. Jean Frederic Colombel4,
  4. Clelia Coutzac5,
  5. David Faleck4,
  6. Lysiane Marthey1,
  7. Michael Collins1,2,
  8. Nathalie Chaput5,6,
  9. Caroline Robert2,7,
  10. Franck Carbonnel1,2
  1. 1 Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance Publique- Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France
  2. 2 Faculté de Médecine, University Paris-Saclay, Le Kremlin Bicêtre, France
  3. 3 Micalis Institute, INRA, AgroParisTech, University Paris-Saclay, Jouy-en- Josas, France
  4. 4 Helmsley Inflammatory Bowel Disease Center, Icahn Medical School of Medicine at Mount Sinai, New York, USA
  5. 5 Laboratory of Immunomonitoring in Oncology and CNRS-UMS 3655 and INSERM-US23, Villejuif, France
  6. 6 Faculté de Pharmacie, University Paris-Saclay, Chatenay-Malabry, France
  7. 7 Départment of Medecine, Dermatology Unit, Villejuif, France
  1. Correspondence to Dr Franck Carbonnel, Department of Gastroenterology, Kremlin Bicêtre Hospital, Le Kremlin Bicêtre 94270, France; franck.carbonnel{at}aphp.fr

Abstract

Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed death-1 (PD-1)/ligand are increasingly used to treat several types of cancer. These drugs enhance antitumour T-cell activity and therefore induce immune-related adverse effects (irAE), of which gastrointestinal (GI) irAE are among the most frequent and severe. This systematic literature review summarises the clinical manifestations, management and pathophysiology of GI irAE due to immune checkpoint inhibitors. GI irAE induced by anti-CTLA-4 are frequent, potentially severe and resemble IBD, whereas those induced by PD-1 blockade seem to be less frequent and clinically more diverse. Baseline symbiotic gut microbiota is associated with an enhanced antitumour response to immune checkpoint inhibitors and an increased susceptibility to developing enterocolitis, in patients treated with anti-CTLA-4. These findings open new perspectives for possible manipulation of the gut microbiota in order to better identify responders to immune checkpoint inhibitors and to increase their efficacy and safety.

  • inflammatory bowel disease
  • immunotherapy
  • colonic microflora

https://doi.org/10.1136/gutjnl-2018-316948

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    Footnotes

    • ES, PL, CR and FC contributed equally.

    • Contributors ES and FC performed the systematic literature review and wrote the first draft of manuscript; JFC and DF contributed to the writing of the manuscript. PL contributed of the acquisition of data and writing of microbiota section. Others contributed to the acquisition of data and critical appraisal of the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests Franck Carbonnel received boards or lecture fees from enterome, MSD, BMS, Janssen, Pfizer, AbbVie, Mayoly Spindler, Takeda, Pileje Jean Frédéric Colombel: Consultant or advisory board member for AbbVie, Amgen, Boehringer-Ingelheim, Arena Pharmaceuticals, Celgene, Celltrion, Enterome, Eli Lilly, Ferring Pharmaceuticals, Genentech, Janssen and Janssen, Medimmune, Merck & Co, Nextbiotix, Novartis Pharmaceuticals, Otsuka Pharmaceutical Development & Commercialization, Pfizer, Protagonist, Second Genome, Gilead, Seres Therapeutics, Shire, Takeda, Theradiag. Speaker for AbbVie, Ferring, Takeda, Celgene. Stock options: Intestinal Biotech Development, Genfit Research grants: AbbVie, Takeda, Janssen and Janssen.

    • Patient consent Not required.

    • Provenance and peer review Commissioned; externally peer reviewed.