Beta-Glucan Enhances Antitumor Immune Responses By Regulating Differentiation And Function Of Monocytic Myeloid-Derived Suppressor Cells

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. -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 -glucans on MDSCs and found that -glucan treatment could promote the differentiation of M-MDSCs (monocytic MDSCs) into a more mature CD11c+ F4/80+ Ly6Clow population via dectin-1 pathway in vitro, which is NF-B dependent, and the suppressive function of M-MDSCs was significantly decreased. Treatment of orally administered yeast-derived particulate -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 -glucans induce the differentiation of MDSCs and inhibit the regulatory function of MDSCs, therefore revealing a novel mechanism for -glucans in immunotherapy and suggesting their potential clinical benefit.