Particulate Yeast‐derived Beta‐Glucan Stimulates Anti‐tumor T Cell Responses via Modulating Tumor Microenvironment toward Th1 Response

Abstract

β‐Glucans are glucose polymers produced by a variety of plants and microorganisms. Previous studies demonstrated that soluble yeast β‐glucans could bind to the lectin site of complement receptor 3 (CR3) and prime leukocyte CR3 to elicit cytotoxicity of iC3b‐opsonized tumors. In this study, we investigated the mechanism of action for particulate yeast β‐glucan in tumor immunotherapy. Both in vitro and in vivo studies showed that particulate β‐glucan, but not soluble β‐glucan, stimulated DCs for up‐regulation of surface accessory molecules and production of cytokines such as IL‐12 and TNF‐α. Orally administered particulate β‐glucan treatment was shown to induce enhanced antigen‐specific CD4 and CD8 T cell responses. Oral particulate β‐glucan treatment also activated tumor‐infiltrating DCs and modulated cytokine profile within the tumor milieu, predominately upregulation of IL‐12 and IFN‐γ secretion. Tumor‐bearing mice treated with particulate β‐glucan alone had a significant reduced tumor burden with respect to mice treated with saline. The enhanced anti‐tumor responses correlated with increased IFN‐γ‐producing T cells and augmented CD8 T cell‐mediated cytotoxic activity. Taken together, we demonstrate that particulate β‐glucan has its unique function in eliciting potent anti‐tumor adaptive immune responses via regulating the tumor microenvironment. (This work was supported by NIH/NCI RO1 CA86412)