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- W4205125855 abstract "Abstract Background & 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 . PD-L1 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." @default.
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- W4205125855 date "2022-01-20" @default.
- W4205125855 modified "2023-10-17" @default.
- W4205125855 title "The Immune Microenvironment Features and Response to Immunotherapy in EBV-associated Lymphoepithelioma-like Cholangiocarcinoma" @default.
- W4205125855 doi "https://doi.org/10.21203/rs.3.rs-1259214/v1" @default.
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