[#2010-11] A polysaccharide extracted from Grifola frondosa enhances the anti-tumor activity of bone marrow-derived dendritic cell-based immunotherapy against murine colon cancer, Yuki Masuda et al.

 

Abstract

We previously isolated the novel heteropoly­saccharide maitake Z-fraction (MZF) from the maitake mushroom (Grifola frondosa), and demonstrated that MZF significantly inhibited tumor growth by inducing cell-mediated immunity. In this study, we demonstrated that MZF upregulated the expression of CD80, CD86, CD83, and MHC II on bone marrow-derived dendritic cells (DCs) and significantly increased interleukin-12 (IL-12) and tumor necrosis factor-alpha production by DCs in a dose-dependent manner. MZF-treated DCs significantly stimu­lated both allogeneic and antigen-specific syngenic T cell responses and enhanced antigen-specific interferon-gamma (IFN-y) production by syngenic CD4⁺ T cells; however, MZF-treated DCs did not affect IL-4 production. Further­more, the enhancement of IFN-y production in CD4⁺ T cells, which was induced by MZF-treated DCs, was com­pletely inhibited by the addition of an anti-IL-12 antibody. These results indicate that MZF induced DC maturation and antigen-specific Th1 response by enhancing DC-pro­duced IL-12. We also demonstrated that DCs pulsed with colon-26 tumor lysate in the presence of MZF induced both therapeutic and preventive effects on colon-26 tumor development in BALB/c mice. These results suggest that MZF could be a potential effective adjuvant to enhance immunotherapy using DC-based vaccination.