A polysaccharide extracted from Grifola frondosa enhances the anti-tumor activity of bone marrow-derived dendritic cell-based immunotherapy against murine colon cancer.
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-gamma) production by syngenic CD4(+) T cells; however, MZF-treated DCs did not affect IL-4 production. Furthermore, the enhancement of IFN-gamma 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.
Masuda
Yuki
Y
Department of Microbial Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyama-Kitamachi, Higashinada-ku, Kobe, 658-8558, Japan. organic@kobepharma-u.ac.jp
Ito
Koichi
K
Konishi
Morichika
M
Nanba
Hiroaki
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000276:immunology*; D003110:Colonic Neoplasms / Q000628:therapy*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D048691:Grifola / Q000737:chemistry*; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D011134:Polysaccharides