Spatial Transcriptomics of human hepatocellular cancer

ABSTRACT: Background: Immune checkpoint inhibition is now standard of care for patients with advanced hepatocellular cancer (HCC) and yet many patients remain resistant to this therapy. The presence of innate immune populations in the tumour microenvironment (TME) have been implicated in regulating the efficacy of these agents. CLEC14A has previously been shown to be upregulated on tumour endothelial cells and we found endothelial upregulation of CLEC14A in a subset of HCC tumours as well as acute liver injuries. This led us to explore the role of CLEC14A in neutrophil recruitment, critical populations in both liver pathologies. Methods:Immunohistochemical analysis was undertaken of CLEC14A in human liver tissue across a range of liver diseases and HCC. CLEC14A regulation and function was then explored in primary human liver endothelial cells including responses to shear stress and flow based adhesion assays. Liver injury models were undertaken CLEC14A knockout mice followed by intravital microscopy. Finally, CLEC14A expression was studied in both publically available HCC data sets and through spatial transcriptomics of HCC tissue. Findings:We found that CLEC14A mediates neutrophil recruitment across liver endothelium in both in vitro and in vivo settings. This process appears to be independent of its interaction with its known ligand Multimerin-2. Additionally, we demonstrated a correlation of CLEC14A expression in human HCC with a neutrophil transcriptional signature. Interpretation:This study unveils a new link between a tumour angiogenic receptor and neutrophil infiltration to the liver and highlights the potential of combining current immunotherapy in HCC with agents targeting the CLEC14A pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253962 | GEO | 2026/03/31

REPOSITORIES: GEO