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Cisplatin promotes the expression level of PD-L1 in the microenvironment of hepatocellular carcinoma through YAP1

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Abstract

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. However, the immune tolerance limits the effect of chemotherapeutic drugs. Therefore, the mechanism of cisplatin in promoting PD-L1 expression by YAP1 was investigated in the present study, and we found that cisplatin increased the expression level of YAP1 in the mouse liver with H22 cells. Meanwhile, cisplatin improved the expression level of PD-L1, IL-1β and CCL2 in the tumor microenvironment. Further, cisplatin also enhanced the expression level of YAP1 in shYAP1 HepG2215 cells. The expression of PD-L1 was decreased by Verteporfin, YAP1 inhibitor, during the treatment of DEN/TCPOBOP-induced liver cancer in C57BL/6 mice. These results suggested that cisplatin could deteriorate the immunosuppressive microenvironment through increasing PD-L1, CCL2, IL-1β by upregulated YAP1 expression. Therefore, the study suggested that YAP1 blockade destroyed the immunosuppressive microenvironment of cancer to improve the effect of chemotherapy in HCC.

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Funding

This work was financially supported by the National Natural Science Foundation of China (81873112), the Project of Natural Fund of Hebei Province (H2017423011), Talent Project Training Funding Project of Hebei Province (A201902015), Hundred Outstanding Innovative Talents Support Program of Universities in Hebei Province (SLRC2019043), and the Research Fund from Hebei Key Laboratory of Integrative Medicine on Liver Kidney Patterns (A201904).

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  1. Shenghao Li and Jingmin Ji have contributed equally to this work.

Authors and Affiliations

  1. Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, No.3 Xingyuan Road, Shijiazhuang, 050200, Hebei, China

    Shenghao Li, Jingmin Ji, Zhiqin Zhang, Qing Peng, Liyuan Hao, Yinglin Guo, Wenhan Zhou, Qingzhuo Cui & Xinli Shi

  2. Hebei Key Laboratory of Integrative Medicine On Liver Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China

    Shenghao Li & Xinli Shi

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  1. Shenghao Li
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XS designed research; SL, JJ, ZZ, QP, LH, YG, WZ, and QC performed the experiments; SL and XS wrote the manuscript with contributions from all authors. All authors read and approved the initial manuscript.

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Correspondence to Xinli Shi.

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Li, S., Ji, J., Zhang, Z. et al. Cisplatin promotes the expression level of PD-L1 in the microenvironment of hepatocellular carcinoma through YAP1. Mol Cell Biochem 475, 79–91 (2020). https://doi.org/10.1007/s11010-020-03861-0

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