Oral administration of soluble β-glucans extracted from Grifola frondosa induces systemic antitumor immune response and decreases immunosuppression in tumor-bearing mice

Int J Cancer. 2013 Jul;133(1):108-19. doi: 10.1002/ijc.27999. Epub 2013 Feb 15.

Abstract

Maitake D (MD)-Fraction is a highly purified soluble β-glucan derived from Grifola frondosa (an oriental edible mushroom). Intraperitoneal (i.p.) injection of MD-Fraction has been reported to inhibit tumor growth via enhancement of the host immune system. In this study, we demonstrated that oral administration of MD-Fraction as well as i.p. injection significantly inhibited tumor growth in murine tumor models. After oral administration, MD-Fraction was not transferred to the blood in its free form but was captured by antigen-presenting cells such as macrophages and dendritic cells (DCs) present in the Peyer's patch. The captured MD-Fraction was then transported to the spleen, thereby inducing the systemic immune response. Our study showed that MD-Fraction directly induced DC maturation via a C-type lectin receptor dectin-1 pathway. The therapeutic response of orally administered MD-Fraction was associated with (i) induced systemic tumor-antigen specific T cell response via dectin-1-dependent activation of DCs, (ii) increased infiltration of the activated T cells into the tumor and (iii) decreased number of tumor-caused immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells. Our preclinical study suggests that MD-Fraction is a useful oral therapeutic agent in the management of patients with cancer.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacology*
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Female
  • Flow Cytometry
  • Grifola*
  • Immune Tolerance / drug effects*
  • Immunity, Innate / drug effects*
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation / drug effects
  • Macrophages / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / immunology*
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • beta-Glucans / administration & dosage
  • beta-Glucans / blood
  • beta-Glucans / pharmacology*

Substances

  • Antineoplastic Agents
  • Cytokines
  • Lectins, C-Type
  • beta-Glucans
  • dectin 1