Open AccessNorcantharidin enhances antitumor immunity of GM ‐ CSF prostate cancer cells vaccine by inducing apoptosis of regulatory T cells
Author(s) -
Mo Lijun,
Zhang Xinji,
Shi Xiaojun,
Wei Lili,
Zheng Dianpeng,
Li Hongwei,
Gao Jimin,
Li Jinlong,
Hu Zhiming
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13639
Subject(s) - apoptosis , cancer research , immunity , in vivo , medicine , immunology , immune system , prostate cancer , cancer vaccine , cancer , pharmacology , immunotherapy , biology , biochemistry , microbiology and biotechnology
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 in vitro study showed that NCTD induced apoptosis and inhibited proliferation of regulatory T cells (Tregs). Mechanistic research showed that NCTD inhibited Akt activation and activated FOXO 1 transcription, resulting in a pro‐apoptotic effect. The results of the in vivo 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 CD 4 + and CD 8 + 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.