Clinicopathologic features, tumor immune microenvironment and genomic landscape of Epstein-Barr virus-associated intrahepatic cholangiocarcinoma

作者：Yuhua Huang, Chris Zhiyi Zhang, Qunsheng Huang, Joe Poh Sheng YEONG, Fang Wang, Xia Yang, Yangfan He, Xiaolong Zhang, Hua Zhang, Shi‐Lu Chen, Yinli Zheng, Ru Deng, Censhan Lin, Mingming Yang, Yan Li, Chen Jiang, Terence K. Lee, Stephanie Ma, Mu‐Sheng Zeng, Jing‐Ping Yun · 发表于：Journal of Hepatology · 年份：2020 · DOI：10.1016/j.jhep.2020.10.037 · 被引用次数：116 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Viral-associated cancers and disorders、Liver Diseases and Immunity

BACKGROUND & AIMS: Little is known about Epstein-Barr virus (EBV)-associated intrahepatic cholangiocarcinoma (EBVaICC) because of its rarity. We aimed to comprehensively investigate the clinicopathology, tumor immune microenvironment (TIME) and genomic landscape of this entity in southern China. METHODS: We evaluated 303 intrahepatic cholangiocarcinomas (ICCs) using in situ hybridization for EBV. We compared clinicopathological parameters between EBVaICC and nonEBVaICC, and we analyzed EBV infection status, tumor-infiltrating lymphocytes (TILs) and genomic features of EBVaICC by immunohistochemistry, double staining, nested PCR, multiplex immunofluorescence staining, fluorescence in situ hybridization and whole-exome sequencing. RESULTS: EBVaICC accounted for 6.6% of ICCs and was associated with EBV latency type I infection and clonal EBV isolates. Patients with EBVaICC were more often female and younger, with solitary tumors, higher HBV infection rates and less frequent cirrhosis; the lymphoepithelioma-like (LEL) subtype was more common in EBVaICC. EBVaICC was associated with a significantly larger TIME component than nonEBVaICC. The LEL subtype of EBVaICC - associated with a significantly increased density and proportion of CD20+ B cells and CD8+ T cells - was associated with significantly higher 2-year survival rates than conventional EBVaICC and nonEBVaICC. Both PD-1 and PD-L1 in TILs, and PD-L1 in tumor cells, were overexpressed in EBVaICC. High PD-L1 expression in tumor...