Current and Emerging Immunotherapy Strategies in Hepatocellular Carcinoma: Standard Treatments and Biomarkers

Immunotherapy has substantially transformed the treatment landscape of advanced hepatocellular carcinoma (HCC).Immune checkpoint inhibitor (ICI)-based combination therapies have shown meaningful survival benefits and are now recommended as first-line systemic treatments for unresectable HCC.Compared with sorafenib in the IMbrave150 trial, the combination of atezolizumab plus bevacizumab demonstrated superior overall survival, progressionfree survival, and objective response rate, thereby establishing a new standard of care.Similarly, the STRIDE regimen, which combines durvalumab plus tremelimumab, has demonstrated improved survival outcomes and durable responses in patients with advanced HCC.Other ICIbased combinations, including nivolumab plus ipilimumab, have exhibited promising clinical activity and are broadening the therapeutic options for this disease.Despite these advances, only a subset of patients achieve durable responses, and treatment outcomes remain heterogeneous.Consequently, considerable efforts have focused on determining predictive biomarkers that guide patient selection for immunotherapy.Numerous candidates have been investigated, including clinical and radiologic features, serum biomarkers (e.g., alpha-fetoprotein dynamics), and tumor molecular characteristics (e.g., PD-L1 expression, T-effector gene signatures, and immune cell infiltration within the tumor microenvironment).However, to date, no single biomarker has yet shown sufficient accuracy or reproducibility for routine clinical use.Therefore, future research should focus on integrated biomarker strategies that combine clinical, radiologic, and molecular information to improve patient stratification and optimize treatment selection.Such precision approaches may improve therapeutic efficacy and further enhance outcomes for patients with advanced HCC.