Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects

Daillere, R., Vetizou, M., Waldschmitt, N., Yamazaki, T., Isnard, C., Poirier-Colame, V., Duong, C. P. M., Flament, C., Lepage, P., Roberti, M. P., Routy, B., Jacquelot, N., Apetoh, L., Becharef, S., Rusakiewicz, S., Langella, P., Sokol, H., Kroemer, G., Enot, D., Roux, A., Eggermont, A., Tartour, E., Johannes, L., Woerther, P. L., Chachaty, E., Soria, J. C., Golden, E., Formenti, S., Plebanski, M., Madondo, M., Rosenstiel, Philip, Raoult, D., Cattoir, V., Boneca, I. G., Chamaillard, M. and Zitvogel, L. (2016) Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects Immunity, 45 (4). pp. 931-943. DOI 10.1016/j.immuni.2016.09.009.

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Supplementary data:


The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX) relies on intestinal bacteria. How and which relevant bacterial species are involved in tumor immunosurveillance, and their mechanism of action are unclear. Here, we identified two bacterial species, Enterococcus hirae and Barnesiella intestinihominis that are involved during CTX therapy. Whereas E. hirae translocated from the small intestine to secondary lymphoid organs and increased the intratumoral CD8/ Treg ratio, B. intestinihominis accumulated in the colon and promoted the infiltration of IFN-gamma-producing gamma delta Tau cells in cancer lesions. The immune sensor, NOD2, limited CTX-induced cancer immunosurveillance and the bioactivity of these microbes. Finally, E. hirae and B. intestinihominis specific-memory Th1 cell immune responses selectively predicted longer progression-free survival in advanced lung and ovarian cancer patients treated with chemo-immunotherapy. Altogether, E. hirae and B. intestinihominis represent valuable ''oncomicrobiotics'' ameliorating the efficacy of the most common alkylating immunomodulatory compound.

Document Type: Article
Additional Information: Times Cited: 2 Daillere, Romain Vetizou, Marie Waldschmitt, Nadine Yamazaki, Takahiro Isnard, Christophe Poirier-Colame, Vichnou Duong, Connie P. M. Flament, Caroline Lepage, Patricia Roberti, Maria Paula Routy, Bertrand Jacquelot, Nicolas Apetoh, Lionel Becharef, Sonia Rusakiewicz, Sylvie Langella, Philippe Sokol, Harry Kroemer, Guido Enot, David Roux, Antoine Eggermont, Alexander Tartour, Eric Johannes, Ludger Woerther, Paul-Louis Chachaty, Elisabeth Soria, Jean-Charles Golden, Encouse Formenti, Silvia Plebanski, Magdalena Madondo, Mutsa Rosenstiel, Philip Raoult, Didier Cattoir, Vincent Boneca, Ivo Gomperts Chamaillard, Mathias Zitvogel, Laurence
Research affiliation: Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
Kiel University
Refereed: Yes
DOI etc.: 10.1016/j.immuni.2016.09.009
ISSN: 1074-7613
Projects: Future Ocean
Date Deposited: 27 Feb 2017 09:25
Last Modified: 19 Dec 2017 12:50
URI: http://eprints.uni-kiel.de/id/eprint/36041

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