As the primary effector cells of adaptive immunity, CD8+ cytotoxic T lymphocytes are responsible for recognizing and eliminating HBV-infected hepatocytes and tumor cells by secreting perforin, granzyme, and interferon-γ (IFN-γ); however, their function is frequently impaired in HCC TME, characterized by exhaustion phenotypes (e.g., overexpression of PD-1, TIM-3, and LAG-3) induced by chronic viral antigen stimulation and immunosuppressive signals (Baudi et al., 2021; Yang et al., 2019; Arvanitakis et al., 2024). This evidence concerns the gene HAVCR2 and hepatocellular carcinoma.