Immunotherapy for transplantation of hepatocellular carcinoma: the next frontier in adjunctive therapy

The increasing success of liver transplantation in hepatocellular carcinoma (HCC) drives an ever-evolving search for innovative strategies to broaden eligible patients' pools. Recent advances in immuno-oncology have turned the spotlight on immune checkpoint inhibitors (ICIs). This review offers an updated overview of ICIs in liver transplantation for HCC, exploring neoadjuvant and adjuvant approaches and addressing unanswered questions on safety, patients' selection, and response predictors.

ICIs have transitioned from being a last-chance therapeutic hope to becoming an integral cornerstone in the treatment of advanced HCC, holding great promise as a compelling option not only to downstage patients for transplantation but also as an alternative strategy in addressing posttransplantation disease recurrence. Despite ongoing refinements in immunotherapeutic agents, the complex molecular pathways involved emphasize the need for a comprehensive approach to integrate immunotherapy in liver transplantation.

Initial concerns about graft rejection, with ICIs as a bridging therapy to liver transplantation, were successfully addressed using adequate immunosuppressants strategies and minimized with a sufficient washout period. Post-liver transplantation disease recurrence remains challenging, requiring a balance between effective therapy and preserving graft function. Emphasis should be placed on clinical trials validating the risk-benefit ratio of ICIs for liver transplantation, guiding appropriate patients' selection, and establishing clear management pathways.