Research Progress on the Role of Immune Checkpoint Inhibitors in Liver Cancer Therapy

Globally, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality and the sixth most common type of cancer, with pronounced therapeutic challenges in the Asia-Pacific region. Its progression is driven by an immunosuppressive tumor microenvironment (TME) linked to hepatitis B and C viruses (HBV/HCV) or metabolic-associated steatohepatitis (MASH).Immune checkpoint inhibitors (ICIs) are a breakthrough treatment for advanced HCC because they reverse T-cell exhaustion by targeting the PD-1/PD-L1 or CTLA-4 pathways. However, single-agent ICIs yield modest efficacy in second-line therapy (15-20% objective response rate [ORR], 12-15 months median overall survival [OS]), limited by TME-mediated immune evasion.Combination therapies now dominate clinical strategies: (1) Immune-targeted regimens (e.g., anti-angiogenics + ICIs) enhance TME immune infiltration, extending median OS to 19.2 months; (2) Dual checkpoint blockade (such as PD-1 + CTLA-4 inhibitors) boosts ORR to 36%, albeit requiring careful management of immune-related toxicities; (3) Immune-local therapy integration (e.g., ablation/radiation + ICIs) leverages antigen release to amplify systemic responses, achieving 90% disease control rates.Despite these advances, persistent hurdles include TME heterogeneity, drug resistance, and region-specific etiologies (e.g., HBV dominance in Asia). Future progress hinges on multi-omics profiling to decipher molecular drivers, development of predictive biomarkers, and personalized immunomodulatory approaches tailored to individual TME landscapes and etiological factors. Addressing these challenges may unlock more durable responses in this heterogeneous malignancy.