HGF/c‐MET pathway contributes to cisplatin‐mediated PD‐L1 expression in hepatocellular carcinoma
Zhansheng Zhang, Ruohan Yang, Xin Yao, Yue‐Ying Cheng, Hong‐Xiang Shi, Chao‐Yan Yao, Zixuan Gao, Defei Qi, Wenke Zhang, Yuanyuan Dou, Juan Guo, Meng‐Wen Hu, Hui Zhao, Dong Fang
Abstract
Abstract Cisplatin has been reported to promote the expression of programmed cell death ligand‐1 (PD‐L1) in some cancer cells. However, the underlying mechanism through which PD‐L1 is transcriptionally regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p‐Akt, p‐ERK, and PD‐L1 was increased in cisplatin‐treated SNU‐368 and SNU‐739 cells. HGF stimulation also increased PD‐L1 expression in these cells. Moreover, Inhibition of HGF/c‐MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF‐induced PD‐L1 expression in SNU‐368 and SNU‐739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8 + T cells in the tumor. Taken together, our study suggested that HGF/c‐Met axis‐induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin‐mediated PD‐L1 expression. These findings may provide an alternative avenue for the treatment of HCC.