title: Fine-Tuning Cancer Immunotherapy: Optimizing the Gut Microbiome.
abstract: The equilibrium linking the intestinal microbiota, the intestinal epithelium, and the host immune system establishes host health and homeostasis, with perturbations of this balance resulting in chronic inflammatory and autoimmune immunopathologies. The mutualistic symbiosis between gut microbiota and host immunity raises the possibility that dysbiosis of the intestinal content also influences the outcome of cancer immunotherapy. Here, we present our recent findings that specific gut-resident bacteria determine the immunotherapeutic responses associated with CTLA-4 checkpoint blockade. This new evidence hints that interindividual differences in the microbiome may account for the significant heterogeneity in therapeutic and immunopathologic responses to immune checkpoint therapies. We discuss how this new understanding could improve the therapeutic coverage of immune checkpoint inhibitors, and potentially limit their immune-mediated toxicity, through the use of adjunctive "oncomicrobiotics" that indirectly promote beneficial immune responses through optimizing the gut microbiome. Cancer Res; 76(16); 4602-7. ©2016 AACR.
authors.affiliation: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), Villejuif, France. INSERM Unit U1015, Villejuif, France. Université Paris Sud, Université Paris-Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France. laurence.zitvogel@orange.fr jonathan.pitt@gustaveroussy.fr.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Pitt
authors.affiliation: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), Villejuif, France. INSERM Unit U1015, Villejuif, France. Université Paris Sud, Université Paris-Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vétizou
authors.affiliation: Université Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Waldschmitt
authors.affiliation: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), Villejuif, France. INSERM Unit U1015, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Université Pierre et Marie Curie, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France. Center of Clinical Investigations CICBT1428, Gustave Roussy Cancer Campus, 94805, Villejuif, France. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. Department of Women's and Children's Health, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: Université Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.
authors.forename: Mathias
authors.initials: M
authors.lastname: Chamaillard
authors.affiliation: Institut Pasteur, Unit of Biology and Genetics of the Bacterial Cell Wall, Paris, France. INSERM, Equipe Avenir, Paris, France.
authors.forename: Ivo Gomperts
authors.initials: IG
authors.lastname: Boneca
authors.affiliation: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), Villejuif, France. INSERM Unit U1015, Villejuif, France. Université Paris Sud, Université Paris-Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France. Center of Clinical Investigations CICBT1428, Gustave Roussy Cancer Campus, 94805, Villejuif, France. laurence.zitvogel@orange.fr jonathan.pitt@gustaveroussy.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
mesh_terms: D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000639:trends*; D009369:Neoplasms / Q000382:microbiology*