Novel insights into HBV-hepatocellular carcinoma at single-cell sequencing

A significant proportion of hepatocellular carcinoma (HCC) is pathologically associated with hepatitis B virus (HBV) infection, followed by unsatisfied clinical outcomes. The increasing unmet need for HBV-associated hepatocellular carcinoma (HBV-HCC) treatment drives to deeper understand the role of the intricate immune microenvironment, tumor cell plasticity and dynamics of tumor evolution in HBV-associated hepatic carcinogenesis. Thus, a comprehensive understanding of cross-talk between HBV, host cells, and tumor microenvironment is of fundamental importance for identifying immune imbalance and heterogeneity in HBV-HCC. Over the past 5 years, the application of single-cell RNA sequencing (scRNA-seq) in the understanding of heterogeneity and dynamics of immune cells, clonal evolution, and cancer stem cell (CSC) subsets of tumor cells has established a landscape for HBV-HCC tumor ecosystem. Novel insights into anatomizing immune escape mechanisms and tumor drug resistance have remarkably facilitated the revolution of HBV-HCC clinical treatment. Here, we provided a summary of HCC at single-cell resolution and details on the basic workflow, limitations, and improvements of scRNA-seq. The review highlights novel insights derived from scRNA-seq on advances in the immune microenvironment and tumor heterogeneity of HBV-HCC.