Cisplatin Inhibits Bladder Cancer Proliferation Through cGAS-STING Pathway.

Research Square (Research Square)(2020)

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摘要
Background Cisplatin is a commonly used adjuvant chemotherapy for advanced bladder cancer, but its immune related mechanism is still unclear. Exploration the immune effects of cisplatin in bladder cancer would complement the comprehensive mechanism of cisplatin and provide the basis for combination therapy of cisplatin and immunotherapy in bladder cancer. Methods We confirmed the immune effects of cisplatin on T24 and TCCSUP bladder cancer cell lines in vitro and exploration the important function of these immune effects in bladder cancer microenvironment in mice tumor model. Results We found cisplatin induced immune response in bladder cancer by RNA sequencing, and validated cGAS-STING signal was deeply involved in this response. Cisplatin induced cGAS-STING signal inhibited the proliferation of bladder cancer and increased the infiltration percentages of CD8 + T cells and dendritic cells in transplantation mice tumor model. Accumulation of dsDNA and the release of chromatin bound cGAS are important to activate downstream STING. Conclusion Our findings indicated a cisplatin related immune effects in bladder cancer, cisplatin combined with immunotherapy might have a synergistic effect for bladder cancer therapy.
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关键词
bladder cancer,cgas-sting
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