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

Maitake D (MD)-Fraction is a highly purified soluble [beta]-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. What's new? [beta]-Glucans are naturally occurring carbohydrates found in fungi and mushrooms. Injection of a b-glucan called "MD-Fraction" has been found to enhance immune function and inhibit tumor growth. In this study, the authors found that when MD-Fraction was given orally, it significantly inhibited tumor growth in mice. Transported via Peyer's patches, the MD Fraction induced a systemic T cell response and decreased immunosuppressive elements. These findings highlight the potential of MD-Fraction for use as an oral therapeutic agent in the management of patients with cancer. [PUBLICATION ABSTRACT]