Abstract

Microbes and their byproducts have been reported to regulate host health and immune functions. Here we demonstrated that microbial exopolysaccharide produced by Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (EPS-R1) induced CCR6+ CD8+ T cells of mice and humans. In mice, ingestion of EPS-R1 augmented anti-tumor effects of anti-CTLA-4 or anti-PD-1 mAb against CCL20-expressing tumors, in which infiltrating CCR6+ CD8+ T cells were increased and produced IFN-gamma accompanied by a substantial immune response gene expression signature maintaining T cell functions. Of note, the anti-tumor adjuvant effect of EPS-R1 was also observed in germ-free mice. Furthermore, the induction of CCR6 expression was mediated through the phosphorylated structure in EPS-R1 and a lysophosphatidic acid (LPA) receptor on CD8+ T cells. Overall, we find that dietary EPS-R1 consumption induces CCR6+ CD8+ T cells in Peyer's patches, favoring a tumor microenvironment that augments the therapeutic effect of immune checkpoint blockade depending on CCL20 production by tumors.

Authors	Kawanabe-Matsuda, Hirotaka; Takeda, Kazuyoshi; Nakamura, Marie; Makino, Seiya; Karasaki, Takahiro; Kakimi, Kazuhiro; Nishimukai, Megumi; Ohno, Tatsukuni; Omi, Jumpei; Kano, Kuniyuki; Uwamizu, Akiharu; Yagita, Hideo; Gomperts Boneca, Ivo; Eberl, Gerard; Aoki, Junken; Smyth, Mark J; Okumura, Ko
Journal	CANCER DISCOVERY
Pages	1336-1355
Volume	12
Date	1/01/2022
Grant ID
Funding Body
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1158/2159-8290.CD-21-0929