Immunological Crossroads: Optimizing Antirejection Regimens to Sustain Antitumor Immunity in Liver Transplant Recipients with Hepatocellular Carcinoma

Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC). However, lifelong immunosuppressive therapy required to prevent graft rejection inevitably compromises antitumor immunity, thereby increasing the risk of HCC recurrence and metastasis, particularly common in the lungs. This review delves into the complex dynamic equilibrium between immune cell subsets mediating rejection and antitumor immunity, systematically analyzes the impact of current immunosuppressive regimens on this balance, and highlights emerging strategies aimed at minimizing rejection while preserving or enhancing antitumor efficacy. These strategies include immunosuppressive regimen optimization, such as mTOR inhibitor application and calcineurin inhibitor (CNI) minimization, novel immunotherapies, including immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT), and immune tolerance induction. This review also summarizes advances in biomarker research guiding immunosuppressant withdrawal, aiming to provide a theoretical basis and clinical insights for personalized immunotherapy strategies and comprehensive tumor management in LT recipients with HCC.