Liver transplantation (LT) has emerged as a curative strategy for
hepatocellular carcinoma (HCC), but contributes to a higher predisposition to HCC recurrence in the immunosuppression context, especially for
tumors beyond the Milan criteria. Although
immunotherapy has dramatically improved survival for immunocompetent patients and has become the standard of care for a variety of
tumors, including HCC, it is mainly used outside the scope of
organ transplantation owing to potentially fatal allograft rejection. Nevertheless, accumulative evidence has expanded the therapeutic paradigms of
immunotherapy for HCC, from downstaging or bridging management in the pretransplant setting to the salvage or adjuvant strategy in the posttransplant setting. Generally,
immunotherapy mainly includes
immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT) and vaccine therapy. ICIs, followed by ACT, have been most investigated in LT, with some promising results. Because of the complex tumor microenvironment and immunoreactivity when
immunosuppressants are combined with
immunotherapy, it is difficult to reach formulations for
immunosuppressant adjustment and the optimal selection of
immunotherapy as well as patients. In addition, the absence of effective
biomarkers for identifying rejection and
tumor response is still an unresolved barrier to successful clinical
immunotherapy applications for LT. In this review, we comprehensively summarize the available evidence of
immunotherapy used in LT that is specific to HCC. Moreover, we discuss clinically concerning issues regarding the concurrent goals of graft protection and antitumor response.