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^*

^*Corresponding author for this work

Graduate School of Advanced Science and Engineering

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

547 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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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. ",

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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

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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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