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

110 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 - Jan 2019
Externally publishedYes

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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