title: Soluble β-glucan from Grifola frondosa induces tumor regression in synergy with TLR9 agonist via dendritic cell-mediated immunity.
abstract: The maturation of dendritic cells into more-immunostimulatory dendritic cells by stimulation with different combinations of immunologic agents is expected to provide efficient, adoptive immunotherapy against cancer. Soluble β-glucan maitake D-fraction, extracted from the maitake mushroom Grifola frondosa, acts as a potent immunotherapeutic agent, eliciting innate and adoptive immune responses, thereby contributing to its antitumor activity. Here, we evaluated the efficacy of maitake D-fraction, in combination with a Toll-like receptor agonist, to treat tumors in a murine model. Our results showed that maitake D-fraction, in combination with the Toll-like receptor 9 agonist, cytosine-phosphate-guanine oligodeoxynucleotide, synergistically increased the expression of dendritic cell maturation markers and interleukin-12 production in dendritic cells, but it did not increase interleukin-10 production, generating strong effector dendritic cells with an augmented capacity for efficiently priming an antigen-specific, T helper 1-type T cell response. Maitake D-fraction enhances cytosine-phosphate-guanine oligodeoxynucleotide-induced dendritic cell maturation and cytokine responses in a dectin-1-dependent pathway. We further showed that a combination therapy using cytosine-phosphate-guanine oligodeoxynucleotide and maitake D-fraction was highly effective, either as adjuvants for dendritic cell vaccination or by direct administration against murine tumor. Therapeutic responses to direct administration were associated with increased CD11c(+) dendritic cells in the tumor site and the induction of interferon-γ-producing CD4(+) and CD8(+) T cells. Our results indicate that maitake D-fraction and cytosine-phosphate-guanine oligodeoxynucleotide synergistically activated dendritic cells, resulting in tumor regression via an antitumor T helper cell 1-type response. Our findings provide the basis for a potent antitumor therapy using a novel combination of immunologic agents for future clinical immunotherapy studies in patients.
authors: Department of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Higashinada-ku, Kobe 658-8558, Japan organic@kobepharma-u.ac.jp.
authors: Yuki
authors: Y
authors: Masuda
authors: Department of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Higashinada-ku, Kobe 658-8558, Japan.
authors: Daiki
authors: D
authors: Nawa
authors: Department of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Higashinada-ku, Kobe 658-8558, Japan.
authors: Yoshiaki
authors: Y
authors: Nakayama
authors: Department of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Higashinada-ku, Kobe 658-8558, Japan.
authors: Morichika
authors: M
authors: Konishi
authors: Department of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Higashinada-ku, Kobe 658-8558, Japan.
authors: Hiroaki
authors: H
authors: Nanba
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004357:Drug Synergism; D005260:Female; D048691:Grifola / Q000737:chemistry*; D007111:Immunity, Cellular / Q000187:drug effects*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000819:agonists / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000276:immunology; D047071:beta-Glucans / Q000819:agonists / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C408982:CPG-oligonucleotide; C556062:IL10 protein, mouse; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D047071:beta-Glucans; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: CpG ODN; dectin-1; immunotherapy; maitake