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Immunity. 2016 Oct 18;45(4):931-943. doi: 10.1016/j.immuni.2016.09.009. Epub 2016 Oct 4.

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

Author information

1
Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, 94805, France; Institut National de la Santé Et de la Recherche Medicale (INSERM), U1015, GRCC, Villejuif, 94805, France; University of Paris-Saclay, Kremlin Bicêtre, 94270, France.
2
University Lille, CNRS, Inserm, CHRU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL, Centre d'Infection et d'Immunité de Lille, 59000 Lille, France.
3
Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, 94805, France; Institut National de la Santé Et de la Recherche Medicale (INSERM), U1015, GRCC, Villejuif, 94805, France.
4
Université de Caen Basse-Normandie, EA4655 U2RM (Équipe Antibio-Résistance), Caen, 14033, France; CHU de Caen, Service de Microbiologie, Caen, 14033, France.
5
Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, 94805, France; Institut National de la Santé Et de la Recherche Medicale (INSERM), U1015, GRCC, Villejuif, 94805, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, 94805, France.
6
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
7
Lipids, Nutrition, Cancer, INSERM, U866, Dijon, 21078, France; Department of Medicine, Université de Bourgogne Franche-Comté, Dijon, 21078, France; Department of Oncology, Centre Georges François Leclerc, Dijon, 21000, France.
8
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France; AVENIR Team Gut Microbiota and Immunity, ERL, INSERM U 1157/UMR 7203, Faculté de Médecine, Saint-Antoine, Université Pierre et Marie Curie (UPMC), Paris, 75012, France; Service de Gastroentérologie, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (APHP), Paris, 75012, France.
9
INSERM U848, 94805 Villejuif, France; Metabolomics Platform, Institut Gustave Roussy, Villejuif, 94805, France; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138, Paris, 75006, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, 75015, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, 75006, France; Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, 17176, Sweden.
10
Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, 94805, France; Metabolomics Platform, Institut Gustave Roussy, Villejuif, 94805, France.
11
Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, 94805, France; Institut National de la Santé Et de la Recherche Medicale (INSERM), U1015, GRCC, Villejuif, 94805, France; University of Paris-Saclay, Kremlin Bicêtre, 94270, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, 75006, France.
12
Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, 94805, France; University of Paris-Saclay, Kremlin Bicêtre, 94270, France.
13
INSERM U970, Paris Cardiovascular Research Center, Université Paris-Descartes, Sorbonne Paris Cité, Paris, 75015, France; Service d'immunologie biologique, Hôpital Européen Georges Pompidou, Paris, 75015 France.
14
INSERM U1143, 75005 Paris, France; Institut Curie, PSL Research University, Endocytic Trafficking and Therapeutic Delivery group, Paris, 75248, France; CNRS UMR 3666, Paris, 75005, France.
15
Service de microbiologie, GRCC, Villejuif, 94805, France.
16
Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA.
17
Department of Immunology and Pathology, Monash University, Alfred Hospital Precinct, Melbourne, Prahran, Victoria 3181, Australia.
18
Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
19
AIX MARSEILLE UNIVERSITE, URMITE (Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes), UMR 7278, INSERM 1095, IRD 198, Faculté de Médecine, Marseille 13005, France.
20
Université de Caen Basse-Normandie, EA4655 U2RM (Équipe Antibio-Résistance), Caen, 14033, France; CHU de Caen, Service de Microbiologie, Caen, 14033, France; CNR de la Résistance aux Antibiotiques, Laboratoire Associé Entérocoques, Caen, 14033, France.
21
Institut Pasteur, Unit Biology and Genetics of the bacterial Cell Wall, Paris, 75015, France.
22
Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, 94805, France; Institut National de la Santé Et de la Recherche Medicale (INSERM), U1015, GRCC, Villejuif, 94805, France; University of Paris-Saclay, Kremlin Bicêtre, 94270, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, 94805, France. Electronic address: laurence.zitvogel@gustaveroussy.fr.

Abstract

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-γ-producing γδT 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.

PMID:
27717798
DOI:
10.1016/j.immuni.2016.09.009
[Indexed for MEDLINE]
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