Multi-Omics Profiling Unveils the Complexity and Dynamics of Immune Infiltrates in Intrahepatic Cholangiocarcinoma

Simple Summary ICC is a highly heterogeneous malignancy. Within the TME, there is limited knowledge of immune cells that are closely associated with and interact with ICC. This study used machine learning methods to conduct a more comprehensive analysis of multi-omics data and found that the effect of APCs on activating NK cells was weakened, while the effect of activating T cells was enhanced. At the same time, four distinct subpopulations were identified, thereby revising and constructing an immune sensing and response model for ICC.Abstract Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous malignancy. The reasons behind the global rise in the incidence of ICC remain unclear, and there exists limited knowledge regarding the immune cells within the tumor microenvironment (TME). In this study, a more comprehensive analysis of multi-omics data was performed using machine learning methods. The study found that the immunoactivity of B cells, macrophages, and T cells in the infiltrating immune cells of ICC exhibits a significantly higher level of immunoactivity in comparison to other immune cells. During the immune sensing and response, the effect of antigen-presenting cells (APCs) such as B cells and macrophages on activating NK cells was weakened, while the effect of activating T cells became stronger. Simultaneously, four distinct subpopulations, namely BLp, MacrophagesLp, BHn, and THn, have been identified from the infiltrating immune cells, and their corresponding immune-related marker genes have been identified. The immune sensing and response model of ICC has been revised and constructed based on our current comprehension. This study not only helps to deepen the understanding the heterogeneity of infiltrating immune cells in ICC, but also may provide valuable insights into the diagnosis, evaluation, treatment, and prognosis of ICC.