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+ Ly6Clow 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 particu-
late 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 progres-
sion. 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.
