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

Romain Daillère (1) , Marie Vétizou (1) , Nadine Waldschmitt (2) , Takahiro Yamazaki (1) , Christophe Isnard (3) , Vichnou Poirier-Colame (1) , Connie p.M. Duong (1, 4) , Caroline Flament (1, 4) , Patricia Lepage (5) , Maria paula Roberti (1, 4) , Bertrand Routy (1) , Nicolas Jacquelot (1) , Lionel Apetoh (6, 7) , Sonia Becharef (1, 4) , Sylvie Rusakiewicz (1, 4) , Philip Langella (5) , Harry Sokol (8, 9) , Guido Kroemer (10, 11, 12, 13) , David Enot (14, 10) , Antoine Roux (15, 1) , Alexander Eggermont (14, 2) , Eric Tartour (16) , Ludger Johannes (17) , Paul-Louis Woerther (18) , Elisabeth Chachaty (18) , Jean-Charles Soria (19, 14) , Encouse Golden (20) , Silvia Formenti (20) , Magdalena Plebanski (21) , Mutsa Madondo (21) , Philip Rosenstiel (22) , Didier Raoult (23, 24) , Vincent Cattoir (3, 25) , Ivo gomperts Boneca (26) , Mathias Chamaillard (3) , Laurence Zitvogel (1, 4)

1 UMR 1015 - Immunologie des tumeurs et immunothérapie
2 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
3 U2RM - Unité de Recherche Risques Microbiens
4 CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers
5 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
6 Département d'oncologie médicale [Centre Georges-François Leclerc]
7 LNC - Lipides - Nutrition - Cancer (U866)
8 CHU Saint-Antoine [AP-HP]
9 UPMC - Université Pierre et Marie Curie - Paris 6
10 Plateforme de métabolomique
11 U848 - Apoptose, cancer et immunité
12 CRC - Centre de Recherche des Cordeliers
13 Service de biologie [CHU HEGP]
14 IGR - Institut Gustave Roussy
15 UPD5 - Université Paris Descartes - Paris 5
16 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
17 CBMCT - UMR 3666 / U1143 - Chimie biologique des membranes et ciblage thérapeutique
18 Microbiologie
19 Université Paris-Saclay
20 Department Radiation Oncology (Weill Cornell Medicine)
21 Monash University [Clayton]
22 ULD - Unabhängiges Landeszentrum für Datenschutz Schleswig-Holstein [Kiel, Germany]
23 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
24 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
25 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
26 BGPB - Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall

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.

Mots clés: Intestinal Microbiota; Dendritic Cells; Inflammation; Infection; Richness; Antitumor Immunity; Gut Microbiota; Cancer; Bacteria; Translocation

Domaines: Immunologie

Romain Daillère, Marie Vétizou, Nadine Waldschmitt, Takahiro Yamazaki, Christophe Isnard, et al.. Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects. Immunity, 2016, 45 (4), pp.931 - 943. ⟨10.1016/j.immuni.2016.09.009⟩. ⟨hal-01429856⟩