BRD7 Inhibited Immune Escape in Nasopharyngeal Carcinoma via Inhibiting PD-L1 Expression

BRD7 通过抑制 PD-L1 表达抑制鼻咽癌的免疫逃逸

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作者:Yilin Guo, Jiaxue Lu, Xiaoxu Li, Shiqi Yan, Jieyu Zhou, Ziying Tian, Ying Liu, Nan Li, Qing Zhou, Xiayu Li, Lei Shi, Su Jiang, Mengna Li, Xiao Zhou, Donghai Huang, Zhaoyang Zeng, Songqing Fan, Wei Xiong, Ming Zhou, Guiyuan Li, Wenling Zhang

Abstract

Therapeutic strategies aimed at harnessing anti-tumor immunity are being intensively investigated as they show promising results in cancer treatment. The PD-1/ PD-L1 pathway is an essential target for restoring functional anti-tumor immune response. BRD7 is a candidate tumor suppressor gene and nuclear transcription factor of nasopharyngeal carcinoma (NPC) which was cloned in our laboratory. In this paper, we reported that the candidate tumor suppressor gene BRD7 was strongly associated with good prognosis of NPC patients and negatively regulated PD-L1 expression. In addition, we found that BRD7 down-regulated PD-L1 expression and enhanced the killing function of CD8+ T lymphocytes in NPC cells through binding to p85α via the 485-651 domain and inhibiting the activity of PI3K, thereby inhibiting the activity of PI3K/AKT/mTOR/STAT3 pathway. In vivo experiments, the results showed that BRD7 could not only inhibit the growth of tumors, but also play a better anti-tumor effect when combined with PD-L1 antibody. These results provided further evidence that BRD7 inhibited immune escape of NPC through down-regulating PD-L1 expression.

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