β‐Glucan enhances antitumor immune responses by regulating differentiation and function of monocytic myeloid‐derived suppressor cells

Abstract

Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a major role in tumor-induced immunosuppression, which hampers effective immuno-therapeutic approaches. β-Glucans have been reported to function as potent immuno-modulators to stimulate innate and adaptive immune responses, which contributes to their antitumor property. Here, we investigated the effect of particulate β-glucans on MDSCs and found that β-glucan treatment could promote the differentiation of M-MDSCs (monocytic MDSCs) into a more mature CD11c(+) F4/80(+) Ly6C(low) population via dectin-1 pathway in vitro, which is NF-κB dependent, and the suppressive function of M-MDSCs was significantly decreased. Treatment of orally administered yeast-derived particulate β-glucan drastically downregulated MDSCs but increased the infiltrated DCs and macrophages in tumor-bearing mice, thus eliciting CTL and Th1 responses, inhibiting the suppressive activity of regulatory T cells, thereby leading to the delayed tumor progression. We show here for the first time that β-glucans induce the differentiation of MDSCs and inhibit the regulatory function of MDSCs, therefore revealing a novel mechanism for β-glucans in immunotherapy and suggesting their potential clinical benefit.