RRC ID 54418
Author 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.
Title A defined commensal consortium elicits CD8 T cells and anti-cancer immunity.
Journal Nature
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.
Volume 565(7741)
Pages 600-605
Published 2019-1-1
DOI 10.1038/s41586-019-0878-z
PII 10.1038/s41586-019-0878-z
PMID 30675064
MeSH Adenocarcinoma / immunology* Adenocarcinoma / pathology Adenocarcinoma / therapy* Animals Antigens, CD / metabolism Bacteria / classification* Bacteria / immunology Bacteria / isolation & purification CD8-Positive T-Lymphocytes / cytology CD8-Positive T-Lymphocytes / immunology* Cell Line, Tumor Dendritic Cells / immunology Feces / microbiology Female Gastrointestinal Microbiome / immunology* Healthy Volunteers Histocompatibility Antigens Class I / immunology Humans Integrin alpha Chains / metabolism Interferon-gamma / biosynthesis Interferon-gamma / immunology Listeria monocytogenes / immunology Listeriosis / immunology Listeriosis / microbiology Listeriosis / prevention & control* Male Mice Programmed Cell Death 1 Receptor / antagonists & inhibitors Programmed Cell Death 1 Receptor / immunology Symbiosis / immunology* Xenograft Model Antitumor Assays
IF 43.07
Times Cited 119
Mice RBRC00916 RBRC10034