The co-location of MARCO+ tumor-associated macrophages and CTSE+ tumor cells determined the poor prognosis in intrahepatic cholangiocarcinoma

作者：Guangyu Fan, Changcheng Tao, Lin Li, Tongji Xie, Le Tang, Xiaohong Han, Yuankai Shi · 发表于：Hepatology · 年份：2024 · DOI：10.1097/hep.0000000000001138 · 被引用次数：36 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Immune cells in cancer、Ferroptosis and cancer prognosis

BACKGROUND AND AIMS: Intratumor immune infiltration plays a crucial role in interacting with tumor cells in intrahepatic cholangiocarcinoma (ICC). However, the specific phenotypes of immune cells and their spatial distribution within the tumor microenvironment remain unclear. This study aimed to address these limitations by providing a detailed analysis of immune infiltration patterns in ICC using combined spatial and single-cell transcriptomic data. APPROACH AND RESULTS: We analyzed 29,632 spots from 6 spatial transcriptomic samples and 21,158 cells from 35 single-cell samples of ICC. Two distinct immune infiltration patterns were identified: macrophage+ (characterized by CD68 and macrophage receptor with collagenous structure [MARCO]) and plasma cell+ (characterized by IGHG1 and JCHAIN). These patterns showed contrasting impacts on patient survival, with macrophage+ infiltration associated with poorer outcomes and plasma cell+ infiltration linked to better survival. MARCO+ tumor-associated macrophages (TAMs) were the predominant cell type in macrophage+ samples, indicative of an immune-resistant microenvironment. In MARCO+ TAMs, elevated epithelial-mesenchymal transition activity, angiogenesis, and hypoxia were observed. Spatial transcriptomics and bulk data also revealed co-location of MARCO+ TAMs with cathepsin E (CTSE+) tumor cells, a finding validated by multiplex immunofluorescence in 20 ICC samples. The co-location area was enriched with protumorigenic pathways and su...