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Single-Cell Mapping Reveals MIF-Centered Immunoregulatory Networks in Colorectal Cancer
Marios Gkoris1,2, Ilias Georgakopoulos-Soares1,3, Apostolos Zaravinos1,2
1Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 1516, Cyprus.
Colorectal cancer progression involves complex tumor microenvironment interactions. Macrophage-epithelial cell communication via MIF-CD74 signaling is key, offering potential therapeutic targets.
Area of Science:
- Oncology
- Immunology
- Computational Biology
Background:
- The tumor microenvironment (TME) critically influences colorectal cancer (CRC) progression, involving intricate cellular crosstalk.
- Understanding these interactions at single-cell resolution is vital for deciphering immune suppression and tumor evolution.
Purpose of the Study:
- To map intercellular communication networks within the CRC TME at single-cell resolution.
- To identify key signaling pathways and cellular players driving CRC progression and immune evasion.
Main Methods:
- Analysis of colorectal cancer single-cell RNA sequencing (scRNA-seq) datasets.
- Utilized Seurat for data integration and CellChat for ligand-receptor interaction inference.
- Performed differential gene expression and pathway enrichment analyses.
Main Results:
- Identified significant cellular heterogeneity in the TME, including specific epithelial (CMS2/CMS3), macrophage (SPP1+), T-cell, and B-cell (CXCR4+) subsets.
- Revealed MIF-centered signaling (MIF-CD74-CXCR4, MIF-CD74-CD44) as a predominant axis between tumor cells and immune cells.
- CMS3 epithelial cells showed strong links to macrophages and cytotoxic lymphocytes via MIF- and APP-CD74 pathways.
- Confirmed elevated MIF, CD74, CD44, and SPP1 expression in tumor tissues.
Conclusions:
- Provided a high-resolution map of intercellular communication in the CRC TME.
- Identified MIF-CD74 signaling as a central immunoregulatory hub in CRC.
- Highlighted the potential of MIF-CD74-associated pathways for therapeutic targeting and biomarker development in colorectal cancer.
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