O02 Deep sequencing of HCC endothelium reveals an active role in immunosuppression and highlights the ecto nucleotidase CD73 as a potential therapeutic target

Introduction Overcoming the immunosuppressive microenvironment in HCC is a major challenge. Better understanding of cell specific contribution required to help boost current immunotherapy. Endothelial cells are gatekeeper for immune recruitment and we undertook RNA-sequencing (RNA-seq) purified human endothelium define its tumour HCC. Methods were isolated from liver tissue using validated method Ulex-lectin binding. RNAseq was performed on primary tumours matched non-tumour endothelial cells. To explore upregulation CD73 sequencing data immunohistochemistry cohort Immunofluorescence sinusoidal (LSEC). Results Analysis paired distal samples taken five patients who underwent surgical resection performed. 45 genes identified as being significantly differentially expressed between (adjusted p value <0.05). 41 upregulated 4 downregulated. Pathway analysis revealed 83 pathways that down regulated <0.05) these further grouped into seven key clusters. These clusters all related pathways: leucocyte mediated immunity; toxicity; proliferation; killing; exocytosis; cytokine. We focused which has well-established function. Immunohistochemistry 100 sections confirmed protein present vascular tumours. The pattern expression different compared control, with peri-membranous staining variable staining. also membrane intracellular cultured LSEC dual colour immunofluorescence. Conclusion Transcriptomic demonstrates strong signature. Interestingly majority upregulated, suggesting plays an active role immunosuppression directly targeting could efficacy other immunotherapies. Validating findings, increased cancer specimens. Furthermore, and, given functional immunosuppression, may contribute be promising target