Soluble β-glucan from Grifola frondosa induces tumor regression in synergy with TLR9 agonist via dendritic cell-mediated immunity

Journal of Leukocyte Biology

Yoshiaki Nakayama¹  Daiki Nawa¹  Yuki Masuda¹  Morichika Konishi¹  Hiroaki Nanba¹ 

[1] Department of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Higashinada-ku, Kobe 658-8558, JapanDepartment of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Higashinada-ku, Kobe 658-8558, JapanDepartment of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Higashinada-ku, Kobe 658-8558, Japan

关键词: dectin-1;    CpG ODN;    maitake;    immunotherapy;   

DOI  :  10.1189/jlb.1A0814-415RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown