Single-cell analysis reveals distinct immune characteristics of hepatocellular carcinoma in HBV-positive versus HBV-negative cases

Abstract Infection with the Hepatitis B virus (HBV) is a key risk factor for Hepatocellular carcinoma (HCC) development and progression. It is widely recognized that immunopathological mechanisms are pivotal in developing HBV-related HCC. Nevertheless, the specific mechanisms by which HBV-induced modifications within the tumor microenvironment (TME) contribute to HCC pathogenesis are still not well understood. Here, we utilized single-cell RNA sequencing to analyze and compare the immune landscapes between HBV-positive and HBV-negative HCC. We discovered that HBV infection significantly modifies the immune cell makeup and state, and leads to the suppression and exhaustion of T cells within the TME. Specifically, an increase in SLC4A10+ CD8+ T cells and IFITM3+ macrophages was observed, along with the upregulation of the gene SLC35F1 in various immune cell subtypes. These findings offer valuable insights into the alteration of the immunological microenvironment in HCC associated with HBV infection, suggesting possible targets for immunotherapeutic intervention.