Single-cell analysis reveals distinct immune characteristics of hepatocellular carcinoma in HBV-positive vs. 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 the development of HBV-associated HCC; nevertheless, the specific underlying mechanisms through which HBV-induced modifications within the tumor microenvironment (TME) contribute to HCC pathogenesis have yet to be fully elucidated. In the present study, single-cell RNA sequencing was utilized to analyze and compare the immune landscapes between HBV-positive and HBV-negative HCC. These experiments revealed that HBV infection significantly modifies the composition and state of immune cells, leading to the suppression and exhaustion of T cells within the TME. Specifically, increases in the proportions of SLC4A10⁺ CD8⁺ T cells and IFITM3⁺ macrophages were observed, along with an upregulation of the gene SLC35F1 in various immune cell subtypes. Taken together, these findings have offered valuable insights into the alteration of the immunological microenvironment in HCC that is associated with HBV infection, suggesting possible targets for immunotherapeutic intervention.