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Glucocorticoid receptor regulates PD-L1 and MHC-I in pancreatic cancer cells to promote immune evasion and immunotherapy resistance

Nat Commun. 2021-12; 
Yalan Deng, Xianghou Xia, Yang Zhao, Zilong Zhao, Consuelo Martinez, Wenjuan Yin, Jun Yao, Qinglei Hang, Weiche Wu, Jie Zhang, Yang Yu, Weiya Xia, Fan Yao, Di Zhao, Yutong Sun, Haoqiang Ying, Mien-Chie Hung, Li Ma
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Proteins, Expression, Isolation and Analysis  Proteins were resolved on 4–12% (GenScript, M00654) or 4–20% (GenScript, M00657) precast gradient gels and transferred to a nitrocellulose membrane using the Trans-Blot Turbo Transfer System (Bio-Rad, 1704150) Get A Quote

摘要

Despite unprecedented responses of some cancers to immune checkpoint blockade (ICB) therapies, the application of checkpoint inhibitors in pancreatic cancer has been unsuccessful. Glucocorticoids and glucocorticoid receptor (GR) signaling are long thought to suppress immunity by acting on immune cells. Here we demonstrate a previously undescribed tumor cell-intrinsic role for GR in activating PD-L1 expression and repressing the major histocompatibility complex class I (MHC-I) expression in pancreatic ductal adenocarcinoma (PDAC) cells through transcriptional regulation. In mouse models of PDAC, either tumor cell-specific depletion or pharmacologic inhibition of GR leads to PD-L1 downregulation and MHC-I upregul... More

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