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Integrative Single-Cell and Spatial Transcriptomic Reveals S100A16+ Tumor Endothelial Cells Drive Angiogenesis and Immunosuppression in Hepatocellular Carcinoma - PubMed

9 hours ago
  • #Immunosuppression
  • #Angiogenesis
  • #Hepatocellular carcinoma
  • Identified 6 distinct endothelial cell subpopulations in HCC, with S100A16+ TECs significantly enriched in HCC tissues.
  • S100A16+ TECs signature correlates with shorter overall survival and disease-free survival in HCC patients.
  • S100A16 overexpression promotes endothelial cell proliferation, migration, and tube formation, driving angiogenesis.
  • CCL20 and TGF-β2 identified as key downstream effectors of S100A16+ TECs.
  • S100A16+ TECs promote regulatory T cell (Treg) differentiation, contributing to immunosuppression.
  • Endothelial-specific S100A16 knockout reduces tumor angiogenesis, Tregs infiltration, and HCC growth in mice.
  • High S100A16+ TECs abundance correlates with vascular invasion, immunotherapy resistance, and shorter progression-free survival.
  • S100A16+ TECs represent a potential therapeutic target and biomarker for immunotherapy response prediction in HCC.