biostudies-literatureGe JNatural Science Foundation of Hunan ProvinceNational Natural Science Foundation of China5074-5088https://www.ebi.ac.uk/biostudies/studies/S-EPMC8974435biostudies-literatureUnknown81(19)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 <i>circBART2.2</i> was found to be highly expressed in NPC where it upregulated PD-L1 expression and inhibited T-cell function <i>in vitro</i> and <i>in vivo</i>. <i>circBART2.2</i> 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 <i>circBART2.2</i>, 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 <i>circBART2.2</i> binding to RIG-I is essential for the regulation of PD-L1 and subsequent immune escape in nasopharyngeal carcinoma.Cancer researchEpstein-Barr Virus-Encoded Circular RNA CircBART2.2 Promotes Immune Escape of Nasopharyngeal Carcinoma by Regulating PD-L1.PMC89744352019JJ50872U20A20367817729288197277681803025Zhou MLi GShi LZeng ZGe JWang FGong ZZhang SWang JXiong WXiang BLi XLi YHe YJiang XZhu KGuo CWang YXiong FMo YfalseEpstein-Barr Virus-Encoded Circular RNA CircBART2.2 Promotes Immune Escape of Nasopharyngeal Carcinoma by Regulating PD-L1.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 <i>circBART2.2</i> was found to be highly expressed in NPC where it upregulated PD-L1 expression and inhibited T-cell function <i>in vitro</i> and <i>in vivo</i>. <i>circBART2.2</i> 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 <i>circBART2.2</i>, 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 <i>circBART2.2</i> binding to RIG-I is essential for the regulation of PD-L1 and subsequent immune escape in nasopharyngeal carcinoma.2021-01-01T00:00:00Z2021 Oct2026-05-09T22:16:01.291Z2025-04-04T20:22:25.245ZS-EPMC89744353432124210.1158/0008-5472.CAN-20-4321