Negar Hemmati
Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer-related mortality worldwide. Despite the availability of therapeutic options such as surgical resection, radiofrequency ablation, molecular-targeted agents, and liver transplantation, HCC shows a poor prognosis and limited responsiveness to conventional treatments. The tumour immune microenvironment (TME) influences key processes in HCC, including selection pressure on tumour cells, immune evasion, tumour evolution, treatment resistance, and recurrence. Among immune components within the TME, T cells, dominant among tumour-infiltrating lymphocytes (TIL), exert both suppressive and promotive effects on tumour growth. Thus, T cell-mediated immune responses are fundamental to cancer surveillance and elimination. Research highlights the crucial role of TILs in HCC prognosis, pathogenesis, and immunotherapy. Subpopulations such as Foxp3+ regulatory T cells, CD8+ cytotoxic T cells, and CD3+/CD4+ helper T cells show complex and often contrasting roles. However, the TME often induces T cell exhaustion or dysfunction, facilitating tumour progression and immune evasion. Understanding immune dysregulation is vital for improving anti-tumour immunity and refining T cell function. This review examines TIL subpopulation roles in HCC, emphasising their plasticity and therapeutic relevance. It also covers emerging T cell-based immunotherapies, especially TIL-based adoptive transfer and CAR-T cell therapy, both showing promise in preclinical and early clinical trials. These novel approaches offer new hope for enhancing immune-driven tumour eradication and improving HCC outcomes.