Antitumor activity of orally administered maitake α-glucan by stimulating antitumor immune response in murine tumor

PLoS One. 2017 Mar 9;12(3):e0173621. doi: 10.1371/journal.pone.0173621. eCollection 2017.

Abstract

Maitake α-glucan, YM-2A, isolated from Grifola frondosa, has been characterized as a highly α-1,6-branched α-1,4 glucan. YM-2A has been shown to possess an anti-virus effect in mice; however, it does not directly inhibit growth of the virus in vitro, indicating that the anti-virus effect of YM-2A might be associated with modulation of the host immune system. In this study, we found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma. Orally administered YM-2A enhanced antitumor immune response by increasing INF-γ-expressing CD4+ and CD8+ cells in the spleen and INF-γ-expressing CD8+ cells in tumor-draining lymph nodes. In vitro study showed that YM-2A directly activated splenic CD11b+ myeloid cells, peritoneal macrophages and bone marrow-derived dendritic cells, but did not affect splenic CD11b- lymphocytes or colon-26 tumor cells. YM-2A is more slowly digested by pancreatic α-amylase than are amylopectin and rabbit liver glycogen, and orally administered YM-2A enhanced the expression of MHC class II and CD86 on dendritic cells and the expression of MHC class II on macrophages in Peyer's patches. Furthermore, in vitro stimulation of YM-2A increased the expression of pro-inflammatory cytokines in Peyer's patch CD11c+ cells. These results suggest that orally administered YM-2A can activate dendritic cells and macrophages in Peyer's patches, inducing systemic antitumor T-cell response. Thus, YM-2A might be a candidate for an oral therapeutic agent in cancer immunotherapy.

MeSH terms

  • Adjuvants, Immunologic
  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / immunology
  • Cytokines / metabolism
  • Female
  • Glucans / administration & dosage
  • Glucans / pharmacology*
  • Grifola / chemistry*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Pancreatic alpha-Amylases / metabolism
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / metabolism
  • Tumor Cells, Cultured

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Cytokines
  • Glucans
  • Pancreatic alpha-Amylases

Grants and funding

Yukiguni Maitake Co., Ltd. provided research materials and a research grant for consumables, but did not have any input into the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.