Spatial Transcriptomics of human hepatocellular cancer

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.