Journal Article

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

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

2019

Overview

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. A consortium of 11 bacterial strains from the healthy human gut microbiota can strongly induce interferon-γ-producing CD8 T cells in the intestine, and enhance both resistance to bacterial infection and the therapeutic efficacy of immune checkpoint inhibitors.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/31 / 13/51 / 45/22 / 45/23 / 631/250/347 / 631/326/2565/2134 / 64/60 / Adenocarcinoma - immunology / Adenocarcinoma - pathology / Adenocarcinoma - therapy / Animal models / Animals / Antigens, CD - metabolism / Bacteria - classification / Bacteria - immunology / Bacteria - isolation & purification / Bacterial infections / Biological response modifiers / Cancer / Cancer treatment / CD103 antigen / CD8 antigen / CD8-Positive T-Lymphocytes - cytology / CD8-Positive T-Lymphocytes - immunology / Cell Line, Tumor / Colonization / Consortia / Dendritic cells / Dendritic Cells - immunology / Feces - microbiology / Female / Gastrointestinal Microbiome - immunology / Genes / Health aspects / Healthy Volunteers / Histocompatibility Antigens Class I - immunology / Humanities and Social Sciences / Humans / Immune checkpoint inhibitors / Immunity / Immunotherapy / Inflammation / Integrin alpha Chains - metabolism / Interferon / Interferon-gamma - biosynthesis / Interferon-gamma - immunology / Intestinal microflora / Intestine / Listeria / Listeria monocytogenes / Listeria monocytogenes - immunology / Listeriosis - immunology / Listeriosis - microbiology / Listeriosis - prevention & control / Lymphocytes / Lymphocytes T / Major histocompatibility complex / Male / Melanoma / Metastasis / Mice / Microbiomes / Microbiota / Microbiota (Symbiotic organisms) / multidisciplinary / Physiological aspects / Prevention / Production capacity / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Programmed Cell Death 1 Receptor - immunology / Science / Science (multidisciplinary) / Strains (organisms) / Symbiosis - immunology / T cell receptors / T cells / Therapeutic applications / Tumors / Xenograft Model Antitumor Assays / γ-Interferon