title: Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.
abstract: T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)-specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8(+) T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Sivan
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Leticia
authors.initials: L
authors.lastname: Corrales
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Hubert
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Williams
authors.affiliation: Section of Genetic Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Keston
authors.initials: K
authors.lastname: Aquino-Michaels
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Earley
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Franco W
authors.initials: FW
authors.lastname: Benyamin
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yuk Man
authors.initials: YM
authors.lastname: Lei
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Bana
authors.initials: B
authors.lastname: Jabri
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Alegre
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA. Department of Medicine, University of Chicago, Chicago, IL 60637, USA. tgajewsk@medicine.bsd.uchicago.edu.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000276:immunology*; D001644:Bifidobacterium / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D000069467:Fecal Microbiota Transplantation; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007109:Immunity / Q000235:genetics; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy*; D013559:Symbiosis; D013601:T-Lymphocytes / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; D012336:RNA, Ribosomal, 16S