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

Hepatology, 2024

Fan G., Tao C., Li L., Xie T., Tang L., Han X., Shi Y.

Disease areaApplication areaSample typeProducts
Oncology
Pathophysiology
Tissue Culture Conditioned Medium
Olink Target 96

Olink Target 96

Abstract

Intra-tumor immune infiltration is a crucial element interacting with tumor cells in intrahepatic cholangiocarcinoma (ICC). However, its phenotype and related spatial structure remained elusive. To address these limitations, we undertook a comprehensive study combining spatial data (29,632 spots from six samples) and single-cell data (21,158 cells from 35 samples). We identified two distinct infiltration patterns: macrophage+ (characterized by CD68 and MARCO) and plasma cell+ (characterized by IGHG1 and JCHAIN). The macrophage+ and plasma cell+ signatures showed adverse and favorable roles in ICC patients’ survival, respectively. Notably, MARCO+ tumor-associated macrophage (TAM) was recognized as the main cell type in macrophage+ samples, indicating an immune-resistant microenvironment. Increased epithelial-mesenchymal transition activities, angiogenesis, and hypoxia were observed in MARCO+ TAM. The co-location of MARCO+ TAM and CTSE+ tumor cells was observed in spatial transcriptomics and bulk transcriptomics data, validated by multiplex immunofluorescence performed on twenty ICC samples. The co-location area exhibited similar protumorigenic pathways and suppressed immune response. CTSE exhibited associations with intrahepatic metastasis and vascular invasion. Both MARCO+ TAM and CTSE+ tumor cells were associated with worse survival and patients with high infiltration of two cell types displayed the worst survival. Within the co-location area, the galectin signaling pathway was most active in cell-cell communication, with LGALS9-CD44 identified as the main ligand-receptor pair. This study identified macrophage+ and plasma cell+ intra-tumor immune infiltration patterns and the co-location of MARCO+ TAM and CTSE+ tumor cells as contributors to immune resistance.

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