Dietary Lactobacillus-Derived Exopolysaccharide Enhances Immune-Checkpoint Blockade Therapy.

Area of Science:

• Immunology
• Microbiology
• Cancer Research

Background:

• Microbial metabolites can modulate host immune responses and enhance immunotherapy efficacy.
• Probiotics and their byproducts offer potential as adjuncts to cancer treatments.

Purpose of the Study:

• To investigate the effect of Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 exopolysaccharide (EPS-R1) on immune cells and its potential to augment cancer immunotherapy.
• To elucidate the mechanism by which EPS-R1 influences T cell populations and the tumor microenvironment.

Main Methods:

• Administration of EPS-R1 to mice and human samples.
• Analysis of T cell populations, specifically CCR6+ CD8+ T cells, in Peyer's patches and tumor tissues.
• Assessment of antitumor effects of EPS-R1 in combination with anti-CTLA-4 or anti-PD-1 monoclonal antibodies.
• Investigation of the molecular mechanisms underlying EPS-R1-induced CCR6 expression.

Main Results:

• Dietary EPS-R1 induced CCR6+ CD8+ T cells in both mice and humans.
• EPS-R1 augmented the antitumor efficacy of immune checkpoint blockade (anti-CTLA-4/anti-PD-1) against CCL20-expressing tumors.
• EPS-R1 increased the infiltration of IFNγ-producing CCR6+ CD8+ T cells within tumors, enhancing the immune response.
• The adjuvant effect of EPS-R1 was observed even in germ-free mice, indicating a direct host-mediated mechanism.
• EPS-R1-induced CCR6 expression was linked to its phosphorylated structure and lysophosphatidic acid receptor signaling on CD8+ T cells.

Conclusions:

• Dietary EPS-R1 promotes the induction of CCR6+ CD8+ T cells, improving the tumor microenvironment.
• EPS-R1 acts as an effective adjuvant to immune checkpoint blockade therapy, particularly for tumors that produce CCL20.
• The findings highlight the potential of specific microbial exopolysaccharides in enhancing cancer immunotherapy through immune modulation.