Diosgenin promotes antitumor immunity and PD-1 antibody efficacy against melanoma by regulating intestinal microbiota

Diosgenin, a natural steroidal saponin, can exert antitumor effect by regulating immune function and improving intestinal microbiota. The response to anti-PD-1 immunotherapy is associated with intestinal microbiota and effector T cells in tumor microenvironment. We hypothesize that the modulation of diosgeninon intestinal microbiota can facilitate antitumor immunity and the therapeutic efficacy of PD-1 antibody. In melanoma-bearing C57BL/6 mice, we observed that the anti-melanoma effect of diosgeninrelied more on antitumor immunity than direct tumor inhibition activity evidenced by obvious CD4+/CD8+ T-cell infiltration and IFN-γ expression in tumor tissues, and it could improve the compositions of intestinal microbiota. Antibiotics impaired the therapeutic efficacy and immunity responses of diosgeninthrough disturbing intestinal microbiota, indicating the importance of intestinal microbiota in diosgenin’s in vivo antitumor activity. More importantly, the combined administration of PD-1 antibody with diosgeninaggravated the tumor necrosis and apoptosis by eliciting augmented T-cell responses. Taken together, diosgenincan be used as a microecologicalregulator to induce antitumor immunity and improve the efficacy of immune checkpointantibody, making it more suitable for the treatment of malignant tumors.