Prognostic Value and Potential Immunoregulatory Role of SCARF1 in Hepatocellular Carcinoma

Scavenger receptor class F member 1 (SCARF1) is thought to play an important role in the selective recruitment of CD4⁺ T cells to liver sinusoidal endothelial cells during chronic liver disease. However, the contribution of SCARF1 to hepatocellular carcinoma (HCC) is currently unknown. We utilized publically-available RNA-sequencing data from The Cancer Genome Atlas (TGCA) to explore SCARF1 expression in HCC and correlated it with a number of clinicopathological features. Flow adhesion assays were used to determine the role of SCARF1 in CD4⁺ T cell subset recruitment. SCARF1 expression was downregulated in HCC tumor tissues, compared to non-tumoral tissues, and loss of SCARF1 expression was associated with poorly differentiated/aggressive tumors. Additionally, higher SCARF1 expression in HCC tumor tissues was highly prognostic of better overall, disease-free and progression-free survival. SCARF1 within HCC was largely associated with tumor endothelial cells and adhesion studies suggested that it played a role in the specific recruitment of proinflammatory CD4⁺ T cells (CD4⁺CD25^-) to HCC tumor tissues. Endothelial SCARF1 expression in tumor biopsies may provide critical prognostic information. Additionally, SCARF1 may also be a novel endothelial target that could help re-programme the microenvironment of HCC by promoting effector T cell tumor infiltration.