A defined commensal consortium elicits CD8 T cells and anti-cancer immunity
(1) Tanoue T (2) Morita S (3) Plichta DR (4) Skelly AN (5) Suda W (6) Sugiura Y (7) Narushima S (8) Vlamakis H (9) Motoo I (10) Sugita K (11) Shiota A (12) Takeshita K (13) Yasuma-Mitobe K (14) Riethmacher D (15) Kaisho T (16) Norman JM (17) Mucida D (18) Suematsu M (19) Yaguchi T (20) Bucci V (21) Inoue T (22) Kawakami Y (23) Olle B (24) Roberts B (25) Hattori M (26) Xavier RJ (27) Atarashi K (28) Honda K
Tanoue and Morita et al. isolated a consortium of 11 bacterial strains from the human microbiome and transplanted them into mice, where they acted together to induce IFNγ+CD8+ T cell accumulation locally (due to chemokine production, T cell proliferation, and antigen recognition) and systemically (possibly due to changes in circulating metabolites). This effect was dependent on CD103+ DCs, which demonstrated enhanced MHC-I expression. Administration of the 11-mix in mice enhanced immunity to infection and tumor growth, and the efficacy of checkpoint blockade. The 11 strains were rare, low-abundance components of the human microbiome.
(1) Tanoue T (2) Morita S (3) Plichta DR (4) Skelly AN (5) Suda W (6) Sugiura Y (7) Narushima S (8) Vlamakis H (9) Motoo I (10) Sugita K (11) Shiota A (12) Takeshita K (13) Yasuma-Mitobe K (14) Riethmacher D (15) Kaisho T (16) Norman JM (17) Mucida D (18) Suematsu M (19) Yaguchi T (20) Bucci V (21) Inoue T (22) Kawakami Y (23) Olle B (24) Roberts B (25) Hattori M (26) Xavier RJ (27) Atarashi K (28) Honda K
Tanoue and Morita et al. isolated a consortium of 11 bacterial strains from the human microbiome and transplanted them into mice, where they acted together to induce IFNγ+CD8+ T cell accumulation locally (due to chemokine production, T cell proliferation, and antigen recognition) and systemically (possibly due to changes in circulating metabolites). This effect was dependent on CD103+ DCs, which demonstrated enhanced MHC-I expression. Administration of the 11-mix in mice enhanced immunity to infection and tumor growth, and the efficacy of checkpoint blockade. The 11 strains were rare, low-abundance components of the human microbiome.
There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-gamma-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103(+) dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.
Author Info:
(1) Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. JSR-Keio University Medical and Chemical Innovation Center, Tokyo, Japan. RIKEN Cen
ter for Integrative Medical Sciences, Yokohama, Japan. (2) Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. (3) Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. (4) Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. (5) RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. Cooperative Major in Advanced Health Science, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan. Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan. (6) Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan. (7) Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. (8) Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. (9) RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. (10) Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. (11) Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. JSR-Keio University Medical and Chemical Innovation Center, Tokyo, Japan. (12) Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. (13) Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. (14) Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana, Kazakhstan. (15) Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan. (16) Vedanta Biosciences, Cambridge, MA, USA. (17) Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA. (18) Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan. (19) Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan. (20) Department of Bioengineering, Program in Biotechnology and Biomedical Engineering, University of Massachusetts Dartmouth, North Dartmouth, MA, USA. (21) Marmoset Research Department, Central Institute for Experimental Animals, Kawasaki, Japan. (22) Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan. (23) Vedanta Biosciences, Cambridge, MA, USA. (24) Vedanta Biosciences, Cambridge, MA, USA. (25) RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. Cooperative Major in Advanced Health Science, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan. Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan. (26) Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. (27) Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. JSR-Keio University Medical and Chemical Innovation Center, Tokyo, Japan. RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. (28) Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. kenya@keio.jp. JSR-Keio University Medical and Chemical Innovation Center, Tokyo, Japan. kenya@keio.jp. RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. kenya@keio.jp.
