Clinicopathologic features, tumor immune microenvironment and genomic landscape of Epstein-Barr virus-associated intrahepatic cholangiocarcinoma
| Autor: | Xia Yang, Jing-Ping Yun, Joe Yeong, Yan Li, Terence Kin Wah Lee, Shi Lu Chen, Yin-Li Zheng, R. Deng, Chris Zhiyi Zhang, Stephanie Ma, Fang Wang, Qun-Sheng Huang, Hua Zhang, Xiaolong Zhang, Cen-Shan Lin, Ming-Ming Yang, Y. Huang, Chen Jiang, Yang-Fan He, Mu Sheng Zeng |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine China Epstein-Barr Virus Infections Herpesvirus 4 Human Programmed Cell Death 1 Receptor CD8-Positive T-Lymphocytes Biology medicine.disease_cause B7-H1 Antigen Virus Cholangiocarcinoma 03 medical and health sciences Lymphocytes Tumor-Infiltrating 0302 clinical medicine Exome Sequencing Tumor Microenvironment medicine Humans Immune Checkpoint Inhibitors Intrahepatic Cholangiocarcinoma CD20 Hepatology medicine.diagnostic_test Middle Aged Prognosis Immunohistochemistry Survival Analysis Epstein–Barr virus Immune checkpoint 030104 developmental biology Bile Duct Neoplasms biology.protein Cancer research Female 030211 gastroenterology & hepatology CD8 Fluorescence in situ hybridization |
| Zdroj: | Journal of Hepatology. 74:838-849 |
| ISSN: | 0168-8278 |
| Popis: | 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 cells and high CD8+ TIL densities were significantly more common in EBVaICC than in nonEBVaICC. Seven genes (MUC4, DNAH1, GLI2, LIPE, MYH7, RP11-766F14.2 and WDR36) were mutated in at least 3 patients. EBVaICC had a different mutational pattern to liver fluke-associated cholangiocarcinoma and HBV-associated ICC. Conclusions EBVaICC, as a subset of ICC, has unique etiological, clinicopathological and genetic characteristics, with a significantly larger TIME component. Paradoxically, patients with EBVaICC could be candidates for immune checkpoint therapy. Lay summary Epstein-Barr virus (EBV) is associated with a subtype of intrahepatic cholangiocarcinoma, with unique clinicopathological and genetic characteristics. The tumor immune microenvironment is also different in this tumor subtype and patients with EBV-associated intrahepatic cholangiocarcinoma may respond well to immune checkpoint inhibitors. |
| Databáze: | OpenAIRE |
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