Immunogenicity remodeling in hepatocellular carcinoma: mechanisms and translational strategies

Hepatocellular carcinoma (HCC) continues to pose a significant global health challenge. In recent years, immunotherapy has emerged as a critical component of HCC treatment, demonstrating encouraging outcomes in a subset of patients. Nevertheless, the overall response rate to immune checkpoint inhibitors (ICIs) remains modest. Deficient immunogenicity and the consequent failure to adequately activate antitumor immunity are widely regarded as central constraints on immunotherapy efficacy. Unlike previous reviews focusing on immune escape or clinical outcomes, this review centers on tumor immunogenicity as the key determinant of immunotherapy response. We systematically summarize the major mechanisms regulating HCC immunogenicity and outline current strategies to enhance and remodel it. By conceptualizing immunogenicity as the principal determinant of immunotherapy efficacy, we propose a unified framework centered on immunogenicity that integrates intrinsic tumor characteristics, microenvironmental regulation, and diverse therapeutic interventions. Within this framework, we highlight representative immunogenicity‑enhancing strategies, including epigenetic restoration of antigen presentation capacity, induction of immunogenic cell death through local or systemic therapies, and vaccine‑based approaches aimed at amplifying antitumor immunity. Collectively, this review offers a systematic and coherent perspective on immune tolerance in HCC through the lens of immunogenicity remodeling, thereby providing a conceptual foundation for the rational design of future immunotherapy strategies.