Epstein-Barr Virus-Encoded Circular RNA CircBART2.2 Promotes Immune Escape of Nasopharyngeal Carcinoma by Regulating PD-L1.
Epstein-Barr Virus-Encoded Circular RNA CircBART2.2 Promotes Immune Escape of Nasopharyngeal Carcinoma by Regulating PD-L1.
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Epstein-Barr病毒编码的环状RNA CircBART2.2通过调节PD-L1促进鼻咽癌的免疫逃逸
DOI：
10.1158/0008-5472.can-20-4321
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发表时间：
2021-10-01
期刊：
影响因子：
11.2
通讯作者：
Zeng Z
中科院分区：
文献类型：
--
作者：
Ge J;Wang J;Xiong F;Jiang X;Zhu K;Wang Y;Mo Y;Gong Z;Zhang S;He Y;Li X;Shi L;Guo C;Wang F;Zhou M;Xiang B;Li Y;Li G;Xiong W;Zeng Z
这项工作表明，circBART2.2与RIG-I的结合对于鼻咽癌中PD-L1的调节和随后的免疫逃逸至关重要。EB病毒（EBV）感染是鼻咽癌（NPC）的一个既定原因，并参与多种恶性表型，包括肿瘤免疫逃逸。EB病毒可编码多种环状RNA（circRNA），但其在鼻咽癌中的生物学功能尚不清楚。在这项研究中，发现EBV编码的circBART2.2在NPC中高度表达，其中它在体外和体内上调PD-L1表达并抑制T细胞功能。circBART2.2通过结合RIG-I的解旋酶结构域并激活转录因子IRF 3和NF-κB来促进PD-L1的转录，从而导致肿瘤免疫逃逸。这些结果阐明了circBART2.2的生物学功能，解释了EBV感染引起免疫逃逸的新机制，为鼻咽癌的免疫治疗提供了新的靶点。这项工作表明，circBART2.2与RIG-I的结合对于鼻咽癌中PD-L1的调节和随后的免疫逃逸至关重要。
This work demonstrates that circBART2.2 binding to RIG-I is essential for the regulation of PD-L1 and subsequent immune escape in nasopharyngeal carcinoma. Epstein–Barr virus (EBV) infection is an established cause of nasopharyngeal carcinoma (NPC) and is involved in a variety of malignant phenotypes, including tumor immune escape. EBV can encode a variety of circular RNAs (circRNA), however, little is known regarding the biological functions of these circRNAs in NPC. In this study, EBV-encoded circBART2.2 was found to be highly expressed in NPC where it upregulated PD-L1 expression and inhibited T-cell function in vitro and in vivo. circBART2.2 promoted transcription of PD-L1 by binding the helicase domain of RIG-I and activating transcription factors IRF3 and NF-κB, resulting in tumor immune escape. These results elucidate the biological function of circBART2.2, explain a novel mechanism of immune escape caused by EBV infection, and provide a new immunotherapy target for treating NPC. This work demonstrates that circBART2.2 binding to RIG-I is essential for the regulation of PD-L1 and subsequent immune escape in nasopharyngeal carcinoma.