Despite the epidemiological association between intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic effects. Therefore, we sought to identify the genomic, proteomic and single cell transcriptomic architecture of HBV-infected ICC tumors.
A cohort of 32 HBV-infected ICC and 89 non-HBV-ICC were characterized using whole-exome sequencing, proteomic analysis, and single cell RNA sequencing.
Proteomic analysis revealed decreased cell-cell junction levels in HBV-ICC patients. The cell-cell junction level had an inverse relationship with EMT program in ICC patients. Analysis of the immune landscape found that more CD8 T cells and Th2 cells were present in HBV-ICC patients. Single cell analysis indicated that TGFβ-signaling related EMT program changes increased in tumor cells of HBV-ICC patients. And ICAM1+ TAMs are correlated with a poor prognosis and contribute to the EMT in HBV-ICC patients. Immune checkpoints analysis indicated the immunosuppressive landscape of CD8 T cells in HBV-ICC patients.
Our findings provide new insights into the behavior of HBV-infected ICC driven by various pathogenic mechanisms involving decreased cell junction levels and increased progression of the EMT program. Our analysis of the immunosuppressive landscape provides mechanistic information useful for the design of efficacious immune-oncology treatments in intrahepatic cholangiocarcinoma.
Clinical trial identification
Legal entity responsible for the study
1.National Natural Science Foundation of China; 2.Natural Science Foundation of Zhejiang Province; 3.\"Hundred Talents Plan (Clinical Medicine)\" Foundation of Zhejiang University.
All authors have declared no conflicts of interest.