MIF-CD74 axis facilitates MDSC infiltration in the tumor microenvironment of pancreatic ductal adenocarcinoma - PubMed
10 hours ago
- #Pancreatic Cancer
- #Tumor Microenvironment
- #Immunosuppression
- Immune checkpoint inhibitors show limited efficacy in pancreatic ductal adenocarcinoma (PDAC).
- The tumor microenvironment (TME) in PDAC is classified into myeloid cell- and T-cell-dominant subtypes, with myeloid subtype linked to poorer outcomes.
- Myeloid-derived suppressor cells (MDSCs) have the highest hazard ratio among myeloid cell types in PDAC.
- Most MDSCs in PDAC tissues express CD74, unlike lymphocytes.
- Macrophage migration inhibitory factor (MIF), a CD74 ligand, is highly expressed in cancer-associated fibroblasts (CAFs) and cancer cells.
- Spatial transcriptomics reveals MIF-CD74+ myeloid cell interactions in CAF-dominant areas of PDAC tissue.
- MIF+ CAFs enhance MDSC migration, induction, and activation.
- In murine models, MIF-expressing PDAC tumors show increased MDSCs and CD74+ M-MDSCs.
- The MIF-CD74 axis drives interactions between MDSCs and CAFs, contributing to an immunosuppressive TME in PDAC.