Epstein–Barr Virus–Encoded Circular RNA CircBART2.2 Promotes Immune Escape of Nasopharyngeal Carcinoma by Regulating PD-L1
Junshang Ge, Jie Wang, Fang Xiong, Xianjie Jiang, Kunjie Zhu, Yian Wang, Yongzhen Mo, Zhaojian Gong, Shanshan Zhang, Yi He, Xiayu Li, Lei Shi, Can Guo, Fuyan Wang, Ming Zhou, Bo Xiang, Yong Li, Guiyuan Li, Wei Xiong, Zhaoyang Zeng
Abstract
Abstract 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. Significance: 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.