國家衛生研究院 NHRI:Item 3990099045/14443
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    题名: The immune microenvironment features and response to immunotherapy in EBV-associated lymphoepithelioma-like cholangiocarcinoma
    作者: Chiang, NJ;Hou, YC;Tan, KT;Tsai, HW;Lin, YJ;Yeh, YC;Chen, LT;Hou, YF;Chen, MH;Shan, YS
    贡献者: National Institute of Cancer Research
    摘要: Background and aims Limited data are available for tumor immune microenvironment (TIME) in Epstein-Barr virus (EBV)-associated lymphoepithelioma-like cholangiocarcinoma (EBV-LELCC), a rare subtype of intrahepatic cholangiocarcinoma (IHCC). We aimed to investigate TIME features in EBV-LELCC and the correlation between the components of TIME and the clinical outcomes. Methods Tumor tissues from five EBV-LELCC cases confirmed through EBER in situ hybridization and five stage-matched conventional IHCC (non-EBV IHCC) cases were collected. These samples were used to evaluate genetic alterations, TIME composition, and PD-L1 expression through ion AmpliSeq comprehensive cancer panel, PanCancer immune profiling panel, immunohistochemistry, and immunofluorescence staining. The correlation between clinical outcomes and TIME components was analyzed in the two EBV-LELCC cases receiving anti-PD-1 treatment. Results The genetic mutations identified in EBV-LELCC were BARD1, CD19, CD79B, EPHA5, KDM5A, MUC6, MUC16, PTEN, RECQL4, TET1, and TNFAIP3. Both CD79B and TNFAIP3 mutations were involved in the NF-kappa B signaling pathway. PD-Ll was highly expressed in tumor-infiltrating immune cells, especially the T cells and macrophages. The TIME of EBV-LELCC displayed abundant immune cell infiltration with a stronger adaptive immune response. Increased Th1 cells, NK CD56(dim) cells, and M1 macrophages, decreased M2 macrophages, exhausted CD8 T cell infiltration, and increased T cell activation signatures in TIME were associated with longer survival. Two patients with metastatic EBV-LELCC had good disease control after anti-PD-1 antibody treatment. A significantly larger TIME component made EBV-LELCCs more sensitive to immune checkpoint blockade (ICB). Conclusion A better understanding of the composition of TIME in EBV-LELCC is critical for predicting the clinical outcomes of ICB treatment.
    日期: 2022-10
    關聯: Hepatology International. 2022 Oct;16(5):1137-1149.
    Link to: http://dx.doi.org/10.1007/s12072-022-10346-3
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1936-0533&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000820127200001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85133216658
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