A polysaccharide extracted from Grifola frondosa enhances the anti-tumor activity of bone marrow-derived dendritic cell-based immunotherapy against murine colon cancer

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-γ) production by syngenic CD4+ T cells; however, MZF-treated DCs did not affect IL-4 production. Furthermore, the enhancement of IFN-γ 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.

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Acknowledgments

We thank Yukiguni Maitake Co., Ltd. for supplying maitake. We also thank F. Yamamoto for supporting our experiment.

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Correspondence to Yuki Masuda.

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Masuda, Y., Ito, K., Konishi, M. et al. A polysaccharide extracted from Grifola frondosa enhances the anti-tumor activity of bone marrow-derived dendritic cell-based immunotherapy against murine colon cancer. Cancer Immunol Immunother 59, 1531–1541 (2010). https://doi.org/10.1007/s00262-010-0880-7

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Keywords

  • Dendritic cells
  • Vaccines
  • Grifola frondosa
  • BRM
  • IL-12