Immune Cells as Potential Targets for Intrahepatic Cholangio-carcinoma: Insights from Mendelian Randomization

Despite extensive research implicating immune cells involvement in intrahepatic cholangiocarcinoma (ICC) development, the causal relationships between them remain elusive. This study aims to investigate the causal link between immune cells and ICC, paving the way for new immunotherapeutic approaches of ICC. A two-sample Mendelian randomization (MR) analysis was employed to establish the causal relationship between 731 immunophenotype and ICC using publicly accessible genome-wide association study (GWAS) genetic data in this study. The analytical method used in this study included inverse variance weighted, MR-Egger, weighted median, Simple mode and Weighted mode. Sensitivity analyses were conducted to assess the horizontal pleiotropy and heterogeneity of the study results. A total of 15 immune cell phenotypes showed positive results through preliminary MR Analysis, and 2 phenotypes with horizontal pleiotropy were excluded after sensitivity analyses. Thus, this study identified 13 immune cell traits as causal relationships associated with ICC, including 4 types of TBNK, 3 types of B cells, 3 types of T cells, 2 types of regulatory T cells, and 1 type of classical dendritic cells. Our MR study provides evidence for a causal relationship between immune cells and ICC, which may provide a potential foundation for future diagnosis and treatment of ICC.