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PARP1 Suppresses the Transcription of PD-L1 by Poly(ADP-Ribosyl)ating STAT3.

Cancer Immunol Res. 2019; 
DingLing,ChenXi,XuXiaqing,QianYuli,LiangGuikai,YaoFengqi,YaoZhangting,WuHonghai,ZhangJieqiong,HeQiaojun,Ya
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摘要

Studies have pointed to a role of PARP1 in regulating gene expression through poly(ADP-ribosyl)ating, sequence-specific, DNA-binding transcription factors. However, few examples exist that link this role of PARP1 to the immunogenicity of cancer cells. Here, we report that PARP1 poly(ADP-ribosyl)ates STAT3 and subsequently promotes STAT3 dephosphorylation, resulting in reduced transcriptional activity of STAT3 and expression of PD-L1. In this study, we showed that PARP1 silencing or pharmacologic inhibition enhanced the transcription of PD-L1 in cancer cells, which was accompanied by the upregulation of PD-L1 protein expression, both in the cytoplasm and on the cell surface. This induction of PD-... More

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