title: Oral administration of soluble β-glucans extracted from Grifola frondosa induces systemic antitumor immune response and decreases immunosuppression in tumor-bearing mice.
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.
authors.affiliation: Department of Microbial Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyama-kitamachi, Higashinada-ku, Kobe, 658-8558, Japan. organic@kobepharma-u.ac.jp
authors.forename: Yuki
authors.initials: Y
authors.lastname: Masuda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Inoue
authors.forename: Hiroya
authors.initials: H
authors.lastname: Ohta
authors.forename: Ayumi
authors.initials: A
authors.lastname: Miyake
authors.forename: Morichika
authors.initials: M
authors.lastname: Konishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nanba
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D048691:Grifola; D007108:Immune Tolerance / Q000187:drug effects*; D007113:Immunity, Innate / Q000187:drug effects*; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D047071:beta-Glucans / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000099181:Dectin-1
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D037181:Lectins, C-Type; D047071:beta-Glucans; D000099181:Dectin-1