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

The maturation of dendritic cells into moreimmunostimulatory dendritic cells by stimulation with different combinations of immunologic agents is expected to provide efficient, adoptive immunotherapy against cancer. Soluble b-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 Tolllike 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 antigenspecific, 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-g–producing CD4 + and CD8 +