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 journalArticle

161 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 languageEnglish
Pages (from-to)600-605
Number of pages6
JournalNature
Volume565
Issue number7741
DOIs
Publication statusPublished - 2019 Jan 31

ASJC Scopus subject areas

  • General

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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