期刊
CANCER SCIENCE
卷 109, 期 7, 页码 2109-2118出版社
WILEY
DOI: 10.1111/cas.13639
关键词
cancer immunotherapy; mGM-CSF vaccine; norcantharidin; prostate cancer; Tregs
类别
资金
- National Natural Science Foundation of China [81373122, 81672915]
Norcantharidin (NCTD) is a promising antitumor drug with low toxicity. It was reported to be able to regulate immunity, but the mechanism is not yet clear. Here we explored whether NCTD could enhance the antitumor immunity induced by prostate cancer cell vaccine. The results of the invitro study showed that NCTD induced apoptosis and inhibited proliferation of regulatory T cells (Tregs). Mechanistic research showed that NCTD inhibited Akt activation and activated FOXO1 transcription, resulting in a pro-apoptotic effect. The results of the invivo study showed that more tumor-infiltrating Tregs existed within peripheral blood and tumor tissue after treatment with the vaccine. Adding NCTD to vaccine treatment could decrease the number of tumor-infiltrating Tregs and increase the number of CD4(+) and CD8(+) T cells. Combination therapy with NCTD and vaccine was more effective in inhibiting tumor growth than the vaccine alone. In general, this is the first report that NCTD could induce apoptosis of Tregs and enhance the vaccine-induced immunity.
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