Content area
Full text
Introduction
Hepatocellular carcinoma (HCC), a primary liver cancer, presents a significant global health issue, ranking as the sixth most commonly occurring cancer, and the third leading cause of cancer-associated mortality globally (1,2). The incidence of HCC is particularly high in East Asia and sub-Saharan Africa, regions where chronic hepatitis B virus (HBV) infection is endemic (3). HBV is recognized as a significant risk factor in the emergence of HCC. A total of ~300 million individuals are affected by HBV globally, with the virus accounting for almost 50% of all cases of HCC, and virtually all childhood HCC cases (4). Therefore, developing an understanding of the mechanisms via which HBV infection induces HCC is critical for developing effective prevention and treatment strategies, especially for high-risk populations.
One of the critical aspects of HBV infection is its profound impact on the immune microenvironment. The virus has evolved various strategies to evade the host immune system, enabling it to maintain a chronic infection. This evasion is partly achieved via altering the immune microenvironment, which includes the recruitment and modulation of immune cells such as natural killer (NK) cells, T cells and macrophages. These changes can lead to an impaired immune response, enabling the virus to persist and cause ongoing liver damage (5,6).
The immune microenvironment is vital in cancer development. In the context of HBV infection, the altered immune landscape can contribute to the onset and progression of liver cancer. For example, rises in the populations of myeloid-derived suppressor cells and regulatory T cells (Tregs) are often observed, which hinder effective immune responses and support immune tolerance (7,8). On the other hand, the activity of NK cells and cytotoxic T lymphocytes, which are crucial for clearing viral infections, is often diminished (9,10). This dysregulation of immune cell populations may create a tumor-promoting microenvironment. Despite the significant advancements in medical research that have been made (11-14), our understanding of the immune mechanisms via which HBV infection promotes HCC remains poorly understood, largely due to the intricate nature of the immune environment.
Single-cell RNA sequencing (scRNA-seq) has brought about a revolutionary change in terms of how the immune system may be comprehensively analyzed. Its application to immune cell populations has enabled an in-depth characterization of the immune microenvironment, enabling the...