Data from Dietary <i>Lactobacillus</i>-Derived Exopolysaccharide Enhances Immune-Checkpoint Blockade Therapy

Abstract

<div>Abstract<p>Microbes and their byproducts have been reported to regulate host health and immune functions. Here we demonstrated that microbial exopolysaccharide produced by <i>Lactobacillus delbrueckii</i> subsp. <i>bulgaricus</i> OLL1073R-1 (EPS-R1) induced CCR6<sup>+</sup> CD8<sup>+</sup> T cells of mice and humans. In mice, ingestion of EPS-R1 augmented antitumor effects of anti–CTLA-4 or anti–PD-1 monoclonal antibody against CCL20-expressing tumors, in which infiltrating CCR6<sup>+</sup> CD8<sup>+</sup> T cells were increased and produced IFNγ accompanied by a substantial immune response gene expression signature maintaining T-cell functions. Of note, the antitumor 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 receptor on CD8<sup>+</sup> T cells. Overall, we find that dietary EPS-R1 consumption induces CCR6<sup>+</sup> CD8<sup>+</sup> 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.</p>Significance:<p>Gut microbiota- and probiotic-derived metabolites are attractive agents to augment the efficacy of immunotherapies. Here we demonstrated that dietary consumption of <i>Lactobacillus</i>-derived exopolysaccharide induced CCR6<sup>+</sup> CD8<sup>+</sup> T cells in Peyer's patches and improved the tumor microenvironment to augment the therapeutic effects of immune-checkpoint blockade against CCL20-producing tumors.</p><p><i>See related commentary by Di Luccia and Colonna, p. 1189</i>.</p><p><i>This article is highlighted in the In This Issue feature, p. 1171</i></p></div>