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 and Kenya Honda ()
Additional contact information
Takeshi Tanoue: Keio University School of Medicine
Satoru Morita: Keio University School of Medicine
Damian R. Plichta: Broad Institute of MIT and Harvard
Ashwin N. Skelly: Keio University School of Medicine
Wataru Suda: RIKEN Center for Integrative Medical Sciences
Yuki Sugiura: Keio University School of Medicine
Seiko Narushima: Keio University School of Medicine
Hera Vlamakis: Broad Institute of MIT and Harvard
Iori Motoo: RIKEN Center for Integrative Medical Sciences
Kayoko Sugita: Keio University School of Medicine
Atsushi Shiota: Keio University School of Medicine
Kozue Takeshita: Keio University School of Medicine
Keiko Yasuma-Mitobe: Keio University School of Medicine
Dieter Riethmacher: Nazarbayev University School of Medicine
Tsuneyasu Kaisho: Wakayama Medical University
Jason M. Norman: Vedanta Biosciences
Daniel Mucida: The Rockefeller University
Makoto Suematsu: Keio University School of Medicine
Tomonori Yaguchi: Keio University School of Medicine
Vanni Bucci: University of Massachusetts Dartmouth
Takashi Inoue: Central Institute for Experimental Animals
Yutaka Kawakami: Keio University School of Medicine
Bernat Olle: Vedanta Biosciences
Bruce Roberts: Vedanta Biosciences
Masahira Hattori: RIKEN Center for Integrative Medical Sciences
Ramnik J. Xavier: Broad Institute of MIT and Harvard
Koji Atarashi: Keio University School of Medicine
Kenya Honda: Keio University School of Medicine

Nature, 2019, vol. 565, issue 7741, 600-605

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-0878-z

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