A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

Takeshi Tanoue; Satoru Morita; Damian R Plichta; Ashwin N Skelly; Wataru Suda; Yuki Sugiura; Seiko Narushima; Hera Vlamakis; Iori Motoo; Kayoko Sugita; Atsushi Shiota; Kozue Takeshita; Keiko Yasuma-Mitobe; Dieter Riethmacher; Tsuneyasu Kaisho; Jason M Norman; Daniel Mucida; Makoto Suematsu; Tomonori Yaguchi; Vanni Bucci; Takashi Inoue; Yutaka Kawakami; Bernat Olle; Bruce Roberts; Masahira Hattori; Ramnik J Xavier; Koji Atarashi; Kenya Honda

doi:10.1038/s41586-019-0878-z

A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

Nature. 2019 Jan;565(7741):600-605. doi: 10.1038/s41586-019-0878-z. Epub 2019 Jan 23.

Authors

Takeshi Tanoue^{1

2

3}, Satoru Morita¹, Damian R Plichta⁴, Ashwin N Skelly¹, Wataru Suda^{3

5

6}, Yuki Sugiura⁷, Seiko Narushima^{1

3}, Hera Vlamakis⁴, Iori Motoo³, Kayoko Sugita¹, Atsushi Shiota^{1

2}, Kozue Takeshita¹, Keiko Yasuma-Mitobe¹, Dieter Riethmacher⁸, Tsuneyasu Kaisho⁹, Jason M Norman¹⁰, Daniel Mucida¹¹, Makoto Suematsu⁷, Tomonori Yaguchi¹², Vanni Bucci¹³, Takashi Inoue¹⁴, Yutaka Kawakami¹², Bernat Olle¹⁰, Bruce Roberts¹⁰, Masahira Hattori^{3

5

6}, Ramnik J Xavier^{4

15}, Koji Atarashi^{1

2

3}, Kenya Honda^{16

17

18}

Affiliations

¹ Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
² JSR-Keio University Medical and Chemical Innovation Center, Tokyo, Japan.
³ RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁴ Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Cooperative Major in Advanced Health Science, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
⁶ Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
⁷ Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan.
⁸ Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana, Kazakhstan.
⁹ Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
¹⁰ Vedanta Biosciences, Cambridge, MA, USA.
¹¹ Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
¹² Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
¹³ Department of Bioengineering, Program in Biotechnology and Biomedical Engineering, University of Massachusetts Dartmouth, North Dartmouth, MA, USA.
¹⁴ Marmoset Research Department, Central Institute for Experimental Animals, Kawasaki, Japan.
¹⁵ Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹⁶ Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. kenya@keio.jp.
¹⁷ JSR-Keio University Medical and Chemical Innovation Center, Tokyo, Japan. kenya@keio.jp.
¹⁸ RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. kenya@keio.jp.

PMID: 30675064
DOI: 10.1038/s41586-019-0878-z

Abstract

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-γ-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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / immunology*
Adenocarcinoma / pathology
Adenocarcinoma / therapy*
Animals
Antigens, CD / metabolism
Bacteria / classification*
Bacteria / immunology
Bacteria / isolation & purification
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / immunology*
Cell Line, Tumor
Dendritic Cells / immunology
Feces / microbiology
Female
Gastrointestinal Microbiome / immunology*
Healthy Volunteers
Histocompatibility Antigens Class I / immunology
Humans
Integrin alpha Chains / metabolism
Interferon-gamma / biosynthesis
Interferon-gamma / immunology
Listeria monocytogenes / immunology
Listeriosis / immunology
Listeriosis / microbiology
Listeriosis / prevention & control*
Male
Mice
Programmed Cell Death 1 Receptor / antagonists & inhibitors
Programmed Cell Death 1 Receptor / immunology
Symbiosis / immunology*
Xenograft Model Antitumor Assays

Substances

Antigens, CD
Histocompatibility Antigens Class I
Integrin alpha Chains
Programmed Cell Death 1 Receptor
alpha E integrins
Interferon-gamma

Abstract

Publication types

MeSH terms

Substances

Grants and funding