MYC inhibition increases PD-L1 expression induced by IFN-γ in hepatocellular carcinoma cells
MYC inhibition increases PD-L1 expression induced by IFN-γ in hepatocellular carcinoma cells
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MYC 抑制增加 IFN-γ 诱导的肝细胞癌细胞中 PD-L1 的表达
DOI：
10.1016/j.molimm.2018.07.006
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发表时间：
2018
影响因子：
3.6
通讯作者：
Yongyu Shi
中科院分区：
文献类型：
--
作者：
Jiahuan Zou;Mengwei Zhuang;Xiaopeng Yu;Na Li;Rudi Mao;Zhida Wang;Jianing Wang;Xiaoyan Wang;Huaiyu Zhou;Lining Zhang;Yongyu Shi
靶向免疫检查点PD-L1/PD-1通路的免疫疗法的有效性突出了阐明癌细胞中PD-L1表达的调控机制的重要性。先前的研究表明，癌基因MYC上调淋巴瘤中的PD-L1表达。在本研究中，我们研究了MYC在IFN-γ诱导的肝癌细胞PD-L1表达中的调节作用。出乎意料的是，使用siRNA测定敲低MYC表达在mRNA和蛋白质水平上增加了PD-L1的诱导型表达。从机制上讲，MYC的抑制提高了STAT 1的表达，STAT 1是IFN-γ信号通路的关键组分，导致暴露于IFN-γ的HCC细胞中PD-L1表达升高。这些结果表明，MYC可能在HCC的背景下下调PD-L1的表达。本研究表明，针对MYC功能和PD-L1/PD-1通路的联合治疗可能对HCC的治疗有效。
The effectiveness of immunotherapy targeting the immune checkpoint PD-L1/PD-1 pathway highlights importance of elucidating the regulatory mechanisms of PD-L1 expression in cancer cells. Previous studies demonstrate that oncogene MYC up-regulates PD-L1 expression in lymphomas. In the present study, we investigated the regulatory role of MYC in the PD-L1 expression induced by IFN-γ in HCC cells. Unexpectedly, knockdown of MYC expression using siRNA assay increased the inducible expression of PD-L1 both at mRNA and protein levels. Mechanistically, the inhibition of MYC elevated expression of STAT1, a critical component of IFN-γ signaling pathway, leading to the elevation of PD-L1 expression in HCC cells exposed to IFN-γ. These results suggest that MYC may down-regulate PD-L1 expression in the context of HCC. This study implicates that a combination therapy targeting MYC function and PD-L1/PD-1 pathway might be effective for treatment of HCC.