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

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 BucciTakashi Inoue, Yutaka Kawakami, Bernat Olle, Bruce Roberts, Masahira Hattori, Ramnik J. Xavier, Koji Atarashi, Kenya Honda

Research output: Contribution to journal › Article › peer-review

560 Citations (Scopus)

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.

Original language	English
Pages (from-to)	600-605
Number of pages	6
Journal	Nature
Volume	565
Issue number	7741
DOIs	https://doi.org/10.1038/s41586-019-0878-z
Publication status	Published - 2019 Jan 31

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41586-019-0878-z

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Tanoue, T., Morita, S., Plichta, D. R., Skelly, A. N., Suda, W., Sugiura, Y., Narushima, S., Vlamakis, H., Motoo, I., Sugita, K., Shiota, A., Takeshita, K., Yasuma-Mitobe, K., Riethmacher, D., Kaisho, T., Norman, J. M., Mucida, D., Suematsu, M., Yaguchi, T., ... Honda, K. (2019). A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature, 565(7741), 600-605. https://doi.org/10.1038/s41586-019-0878-z

Tanoue, T, Morita, S, Plichta, DR, Skelly, AN, Suda, W, Sugiura, Y, Narushima, S, Vlamakis, H, Motoo, I, Sugita, K, Shiota, A, Takeshita, K, Yasuma-Mitobe, K, Riethmacher, D, Kaisho, T, Norman, JM, Mucida, D, Suematsu, M, Yaguchi, T, Bucci, V, Inoue, T, Kawakami, Y, Olle, B, Roberts, B, Hattori, M, Xavier, RJ, Atarashi, K & Honda, K 2019, 'A defined commensal consortium elicits CD8 T cells and anti-cancer immunity', Nature, vol. 565, no. 7741, pp. 600-605. https://doi.org/10.1038/s41586-019-0878-z

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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.",

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

note = "Funding Information: Acknowledgements K.H. was funded through AMED LEAP under grant number JP18gm0010003, the Takeda Science Foundation, and the Mitsubishi Foundation. T.T. was funded through AMED PRIME under grant number JP18gm6010013 and the Nakajima Foundation. R.J.X. was funded through NIH DK43351, AT009708, and the Center for Microbiome Informatics and Therapeutics, MIT. The LC–MS platform used in this study was provided by the JST ERATO Gas Biology Project, which was led by M.S. until March 2015. We thank N. Palm, J. Faith and J. S. Weber for discussion, J. Baginska and O. Ohara for their technical support, P. Burrows for comments, and RIKEN BRC and the International Mouse Phenotyping Consortium for generating and providing the H2-M3 knockout mice. Publisher Copyright: {\textcopyright} 2019, Springer Nature Limited.",

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T1 - A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

AU - Tanoue, Takeshi

AU - Morita, Satoru

AU - Plichta, Damian R.

AU - Skelly, Ashwin N.

AU - Suda, Wataru

AU - Sugiura, Yuki

AU - Narushima, Seiko

AU - Vlamakis, Hera

AU - Motoo, Iori

AU - Sugita, Kayoko

AU - Shiota, Atsushi

AU - Takeshita, Kozue

AU - Yasuma-Mitobe, Keiko

AU - Riethmacher, Dieter

AU - Kaisho, Tsuneyasu

AU - Norman, Jason M.

AU - Mucida, Daniel

AU - Suematsu, Makoto

AU - Yaguchi, Tomonori

AU - Bucci, Vanni

AU - Inoue, Takashi

AU - Kawakami, Yutaka

AU - Olle, Bernat

AU - Roberts, Bruce

AU - Hattori, Masahira

AU - Xavier, Ramnik J.

AU - Atarashi, Koji

AU - Honda, Kenya

N1 - Funding Information: Acknowledgements K.H. was funded through AMED LEAP under grant number JP18gm0010003, the Takeda Science Foundation, and the Mitsubishi Foundation. T.T. was funded through AMED PRIME under grant number JP18gm6010013 and the Nakajima Foundation. R.J.X. was funded through NIH DK43351, AT009708, and the Center for Microbiome Informatics and Therapeutics, MIT. The LC–MS platform used in this study was provided by the JST ERATO Gas Biology Project, which was led by M.S. until March 2015. We thank N. Palm, J. Faith and J. S. Weber for discussion, J. Baginska and O. Ohara for their technical support, P. Burrows for comments, and RIKEN BRC and the International Mouse Phenotyping Consortium for generating and providing the H2-M3 knockout mice. Publisher Copyright: © 2019, Springer Nature Limited.

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AB - 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.

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

Abstract

ASJC Scopus subject areas

UN SDGs

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