[beta]-glucan restores tumor-educated dendritic cell maturation to enhance antitumor immune responses

Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) in a tumor microenvironment, contributing to tumor escape from immunological attack. Although dendritic cell-based cancer vaccines can initiate antitumor immune responses, tumor-educated dendritic cells (TEDCs) involved in the tolerance induction have attracted much attention recently. In this study, we investigated the effect of [beta]-glucan on TEDCs and found that [beta]-glucan treatment could promote the maturation and migration of TEDCs and that the suppressive function of TEDCs was significantly decreased. Treatment with [beta]-glucan drastically decreased the levels of regulatory T (Treg) cells but increased the infiltration of macrophages, granulocytes and DCs in tumor masses, thus elicited Th1 differentiation and cytotoxic T-lymphocyte responses and led to a delay in tumor progression. These findings reveal that [beta]-glucan can inhibit the regulatory function of TEDCs, therefore revealing a novel function for [beta]-glucan in immunotherapy and suggesting its potential clinical benefit. [beta]-Glucan directly abrogated tumor-educated dendritic cells-associated immune suppression, promoted Th1 differentiation and cytotoxic T-lymphocyte priming and improved antitumor responses. What's new? Yeast-derived [beta]-glucans have been studied extensively for their antitumor effects, and recent investigations suggest that the agents can potently boost innate and adaptive immune responses to undermine tumor growth in the host. The present study adds to that growing body of evidence, showing in cells and mice that yeast-derived [beta]-glucan can restore the function of tumor-associated dendritic cells to enhance antitumor activity. Tumor progression was delayed significantly by [beta]-glucan induction of Th1 differentiation and cytotoxic T-lymphocyte responses. The findings reveal a potential clinical role for [beta]-glucan in cancer immunotherapy.