ArticleHepatology (Baltimore, Md.)2025
The co-location of MARCO+ tumor-associated macrophages and CTSE+ tumor cells determined the poor prognosis in intrahepatic cholangiocarcinoma.
Article in Hepatology (Baltimore, Md.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- HPRT1 drives mitochondrial metabolic reprogramming and immunosuppressive microenvironment in oral squamous cell carcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
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- Advances in the Molecular Mechanisms of Cholangiocarcinoma: A Comprehensive Review of Biomarkers, Regulatory Pathways and Tumor Microenvironment Reprogramming.International journal of molecular sciences · 2026Review
- Pan-cancer single-cell and spatial transcriptomics analyses delineate response-associated heterogeneity and therapeutic targets of tumor-infiltrating B cells following immune checkpoint blockade.Cancer immunology, immunotherapy : CII · 2026Article
- Article
- Spatial single-cell landscape of tumor-associated macrophages and their crosstalk with the tumor microenvironment.Cell discovery · 2026Article
- MARCO promotes cholangiocarcinogenesis by inducing immunosuppression and its targeting reduces tumor growth.Signal transduction and targeted therapy · 2026Article
- A Multi-omics Investigation Identifies TACC3 as a Driver of Immunosuppression in Intrahepatic Cholangiocarcinoma via Activation of the STAT3-PD-L1 Axis.Journal of clinical and translational hepatology · 2026Article
- Identification and characterization of MARCO-expressing tumor-associated macrophages in pancreatic ductal adenocarcinoma with pan-cancer relevance.NPJ precision oncology · 2026Article
- M1 macrophage-targeted engineered ginseng stems and leaves-derived extracellular vesicles delivery system for alleviating rheumatoid arthritis.Regenerative biomaterials · 2026Article
- Spatial immune dysregulation in MASLD: integration of lobular zoning, metabolism and immune function.Frontiers in immunology · 2026Review
- Research progress on the spatiotemporal dynamics of therapy-induced senescence in remodeling the tumor microenvironment.Frontiers in immunology · 2026Review
- Prognostic biomarkers related to PANoptosis in esophageal cancer and their immune microenvironment: multi-omics analysis and therapeutic significance.Frontiers in oncology · 2026Article
- Decoding macrophage heterogeneity in the pulmonary fibrosis lung cancer transition.Frontiers in immunology · 2026Review
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Article
- S100 Calcium-Binding Protein P and Cathepsin E as Key Mediators in Pancreatic Cancer Tumorigenesis.Biomedicines · 2025Article
- Comprehensive Analysis of JCHAIN as a Potential Prognostic Factor for Breast Cancer and an Indicator for Tumor Microenvironment.Biomedicines · 2025Article
- Article
- Histone deacetylases 10 as a prognostic biomarker correlates with tumor microenvironment and therapy response in colorectal cancer.World journal of gastroenterology · 2025Article
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7 authors.
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Abstract
BACKGROUND AND
aimsIntratumor 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
resultsWe 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 suppressed immune responses, and CTSE expression was associated with intrahepatic metastasis and vascular invasion. High infiltration of both MARCO+ TAMs and CTSE+ tumor cells correlated with the poorest survival outcomes. Within the co-location area, the galectin signaling pathway, particularly the LGALS9-CD44 ligand-receptor pair, was highly active in cell-cell communication.
conclusionsThis study identifies 2 intratumor immune infiltration patterns, macrophage+ and plasma cell+, in ICC. Furthermore, the co-location of MARCO+ TAMs and CTSE+ tumor cells contributes to an immune-resistant microenvironment, highlighting potential targets for therapeutic intervention in ICC.
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