title: Oral ingestion of Lentinula edodes mycelia extract can restore the antitumor             T cell response of mice inoculated with colon-26 cells into the subserosal space             of the cecum.
abstract: We previously reported that oral ingestion of Lentinula edodes mycelia (L.E.M.)             extract can inhibit the growth of a subcutaneously established melanoma in a T cell-dependent             manner via mitigation of regulatory T cell (Treg)-mediated immunosuppression.             In this study, we tested the antitumor effect and mechanism of oral ingestion             of L.E.M. extract following inoculation of murine colon carcinoma colon-26 (C26)             cells into the subserosal space of the cecum (i.c.) of syngeneic mice. In this             model, the primary site of the immune response was gut-associated lymphoid tissue             (GALT), which is known to be an immunological tolerance-inducing site for numerous             dietary antigens. Oral ingestion of the L.E.M. extract suppressed the growth of             i.c.-inoculated C26 cells in a T cell-dependent manner and restored the T cell             response of the mesenteric lymph nodes and the spleen, not only to a tumor antigen-derived             peptide, presented on H-2Ld molecules, but also to C26 cells. I.c. inoculation             of C26 cells increased the potential of CD4+ T cells of the mesenteric lymph nodes             to produce transforming growth factor (TGF)-β, but ingestion of the L.E.M. extract             decreased the ability of both CD4+ and CD8+ T cells in the mesenteric lymph nodes             to produce this immunosuppressive cytokine. Although ingestion of L.E.M. showed             only a marginal effect on Tregs in this model, this treatment significantly reduced             the plasma levels of TGF-β and IL-6, both of which were increased in the i.c.             C26-inoculated mice. In summary, our results indicate that oral ingestion of L.E.M.             extract can restore antitumor T cell responses of mice even when the primary antitumor             immune response is elicited in GALT, and provide important implications for anticancer             immunotherapy of human colon cancer.
authors.affiliation: Central R&D Laboratory, Kobayashi Pharmaceutical Co. Ltd., Ibaraki, Osaka, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Matsui
authors.forename: Satoru
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawanishi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Harada
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001688:Biological Products / Q000008:administration & dosage*; D002432:Cecum; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000276:immunology*; D004195:Disease Models, Animal; D004435:Eating; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010455:Peptides / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism; D020942:Shiitake Mushrooms / Q000737:chemistry*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood; D023041:Xenograft Model Antitumor Assays
chemical_list: D001688:Biological Products; D015850:Interleukin-6; D010455:Peptides; D016212:Transforming Growth Factor beta