Molecular Signature and Immune Landscape of HCV-Associated Hepatocellular Carcinoma (HCC): Differences and Similarities with HBV-HCC

To expand our knowledge of the immunologic microenvironment of hepatocellular carcinoma (HCC), we studied the immunologic landscape in liver samples from 20 well-characterized patients with HCC associated with HCV (n=9) or HBV (n=11). For each patient, RNA-sequencing was performed on the tumor and surrounding nontumorous tissue. We found that both HCV- and HBV-HCC are associated with a predominance of downregulated genes. HCV-HCC was characterized by an enrichment of downregulated genes related to T-cell activation and oxidative stress. Conversely, HBV-HCC was characterized by upregulation of genes related to monocyte/macrophage activation and cell cycle control, and downregulation of genes involved in various cell metabolisms. This study demonstrated a distinctive molecular signature and immune landscape in HCC of different viral etiology, which could provide new insights into pathogenesis and lead to the development of novel immune-based therapies.