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Dietary Lactobacillus-derived exopolysaccharide enhances immune checkpoint blockade therapy.

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.