Gut microbiome and anticancer immune response: really hot Sh*t!
The impact of gut microbiota in eliciting innate and adaptive immune responses beneficial for the host in the context of effective therapies against cancer has been highlighted recently. Chemotherapeutic agents, by compromising, to some extent, the intestinal integrity, increase the gut permeability and selective translocation of Gram-positive bacteria in secondary lymphoid organs. There, anticommensal pathogenic Th17 T-cell responses are primed, facilitating the accumulation of Th1 helper T cells in tumor beds after chemotherapy as well as tumor regression. Importantly, the redox equilibrium of myeloid cells contained in the tumor microenvironment is also influenced by the intestinal microbiota. Hence, the anticancer efficacy of alkylating agents (such as cyclophosphamide) and platinum salts (oxaliplatin, cis-platin) is compromised in germ-free mice or animals treated with antibiotics. These findings represent a paradigm shift in our understanding of the mode of action of many compounds having an impact on the host-microbe mutualism.
1] Institut National de la Santé et de la Recherche Médicale, U1015 INSERM, Gustave Roussy, Villejuif, France [2] Université Paris-Sud, Kremlin Bicêtre, France.
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Viaud
1] Institut National de la Santé et de la Recherche Médicale, U1015 INSERM, Gustave Roussy, Villejuif, France [2] Université Paris-Sud, Kremlin Bicêtre, France.
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Daillère
1] Institut Pasteur, Unit Biology and Genetics of the Bacterial Cell Wall, Paris, France [2] Institut National de la Santé et de la Recherche Médicale, Group Avenir, Paris, France.
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Boneca
1] Institut National de la Recherche Agronomique, Micalis UMR1319, Jouy-en-Josas, France [2] AgroParisTech, Micalis UMR1319, 78350 Jouy-en-Josas, France.
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Lepage
1] Institut National de la Recherche Agronomique, Micalis UMR1319, Jouy-en-Josas, France [2] AgroParisTech, Micalis UMR1319, 78350 Jouy-en-Josas, France.
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Langella
1] Université Lille Nord de France, Lille, France [2] Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France [3] Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Lille, France [4] Institut National de la Santé et de la Recherche Médicale, Lille, France.
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Chamaillard
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
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Pittet
1] Institut National de la Santé et de la Recherche Médicale, U866, Centre Georges François Leclerc, Dijon, France [2] Institut National de la Santé et de la Recherche Médicale, Group Avenir, Dijon, France [3] Faculté de Médecine, Université de Bourgogne, Dijon, France.
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Ghiringhelli
Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA.
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Trinchieri
Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA.
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Goldszmid
1] Institut National de la Santé et de la Recherche Médicale, U1015 INSERM, Gustave Roussy, Villejuif, France [2] Université Paris-Sud, Kremlin Bicêtre, France [3] Centre d'Investigation Clinique Biothérapie CICBT 507, Gustave Roussy, Villejuif, France.
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Zitvogel
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D064307:Microbiota / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000382:microbiology*; D058504:Th17 Cells / Q000276:immunology*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents