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Abstract Title:

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

Abstract Source:

Cell Death Dis. 2018 Oct 10 ;9(10):1039. Epub 2018 Oct 10. PMID: 30305604

Abstract Author(s):

Mengxue Dong, Zhefeng Meng, Kudelaidi Kuerban, Feilong Qi, Jiayang Liu, Yuxi Wei, Qian Wang, Shanshan Jiang, Meiqing Feng, Li Ye

Article Affiliation:

Mengxue Dong

Abstract:

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 diosgenin on 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 diosgenin relied more on antitumor immunity than direct tumor inhibition activity evidenced by obvious CD4/CD8T-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 diosgenin through 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 diosgenin aggravated the tumor necrosis and apoptosis by eliciting augmented T-cell responses. Taken together, diosgenin can be used as a microecological regulator to induce antitumor immunity and improve the efficacyof immune checkpoint antibody, making it more suitable for the treatment of malignant tumors.

Study Type : In Vitro Study

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