Gut microbiome and anticancer immune response: really hot Sh(star)t!
2014
Viaud, S. | Daillere, R. | Boneca, I. G. | Lepage, Patricia | Langella, Philippe | Chamaillard, M. | Pittet, M. J. | Ghiringhelli, F. | Trinchieri, G. | Goldszmid, R. | Zitvogel, L. | Immunologie des tumeurs et immunothérapie (UMR 1015) ; Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall (BGPB) ; Institut Pasteur [Paris] (IP) | Groupe Avenir ; Institut National de la Santé et de la Recherche Médicale (INSERM) | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; Institut National de la Recherche Agronomique (INRA)-AgroParisTech | Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL) ; Institut Pasteur de Lille ; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [CHU Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS) | Massachusetts General Hospital [Boston] | Harvard Medical School [Boston] (HMS) | Institut National de la Santé et de la Recherche Médicale (INSERM) | Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL) ; UNICANCER | Université de Bourgogne (UB) | National Cancer Institute [Bethesda] (NCI-NIH) ; National Institutes of Health [Bethesda, MD, USA] (NIH) | Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507) ; Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM) | We thank our colleagues from the Gustave Roussy animal facility and Institut Pasteur axenic mice facility. This work was supported by Institut National du Cancer (INCa), la Ligue contre le cancer (LIGUE labellisée), SIRIC Socrate, LABEX and PACRI Onco-Immunology, European Research Council starting grant (PGN from SHAPE to VIR no. 202283 to IGB) and ISREC Foundation. | ANR-11-PHUC-0002,PACRI,Alliance Parisienne des Instituts de Recherche en Cancérologie(2011) | European Project: 202283,EC:FP7:ERC,ERC-2007-StG,PGNFROMSHAPETOVIR(2008)
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.
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