Abstract 321P
Background
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.
Methods
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).
Results
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 ST 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.
Conclusions
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.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.