TY - JOUR
T1 - The immune microenvironment features and response to immunotherapy in EBV-associated lymphoepithelioma-like cholangiocarcinoma
AU - Chiang, Nai Jung
AU - Hou, Ya Chin
AU - Tan, Kien Thiam
AU - Tsai, Hung Wen
AU - Lin, Yih Jyh
AU - Yeh, Yi Chen
AU - Chen, Li Tzong
AU - Hou, Ya Fu
AU - Chen, Ming Huang
AU - Shan, Yan Shen
N1 - Funding Information:
This work was supported by the Taiwan Ministry of Science and Technology under Grant number MOST 109-2321-B-006-011, MOST 110-2745-B-006-001, and MOST 110-2321-B-006-005; Taiwan Ministry of Health and Welfare under Grant number MOHW110-TDU-B-212-144026, MOHW110-TDU-B-211-124003, and MOHW111-TDU-B-221-014015; and National Health Research Institutes under Grant number NHRI-106A1-PDCO-0217173, NHRI-107A1-CACO-02181811, NHRI-108A1-PDCO-0219193, A1-CAPP23-014, CA-109-PP-23 and CA-110-PP-22.
Funding Information:
We would like to thank Dr. Chien-Feng Li for the assistance in PD-L1 IHC scoring. We also thank the core laboratories of Clinical Medicine Research Center of National Cheng Kung University Hospital for the technical support.
Publisher Copyright:
© 2022, Asian Pacific Association for the Study of the Liver.
PY - 2022/10
Y1 - 2022/10
N2 - 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-κB signaling pathway. 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 CD56dim 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. Graphical abstract: [Figure not available: see fulltext.].
AB - 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-κB signaling pathway. 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 CD56dim 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. Graphical abstract: [Figure not available: see fulltext.].
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U2 - 10.1007/s12072-022-10346-3
DO - 10.1007/s12072-022-10346-3
M3 - Article
C2 - 35780451
AN - SCOPUS:85133216658
VL - 16
SP - 1137
EP - 1149
JO - Hepatology International
JF - Hepatology International
SN - 1936-0533
IS - 5
ER -