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Abstract：
Hepatocellular carcinoma (HCC) remains the leading oncological indication for liver transplantation (LT), with evolving and broadened inclusion criteria. Immune checkpoint inhibitors (ICIs) gained a central role in systemic HCC treatment and showed potential in the peri-transplant setting as downstaging/bridging therapy before LT or as a treatment for HCC recurrence following LT. However, the antagonistic mechanisms of action between ICIs and immunosuppressive drugs pose significant challenges, particularly regarding the risk of acute rejection (AR). This review analyzes the main signaling pathways targeted by ICI therapies and summarizes current studies on ICI therapy before and after LT. The literature on this topic is limited and highly heterogeneous, precluding definitive evidence-based conclusions. The use of ICIs before LT appears promising, provided that a sufficient wash-out period is implemented. In contrast, the results of post-LT ICI therapy do not support its wide clinical application due to high AR rates and overall poor response to treatment. In the future, modern graft preservation techniques might support the selection of good ICI responders, but data from high-level studies are urgently needed.
摘要：
肝细胞癌（HCC）仍然是肝移植（LT）的主要肿瘤适应症，随着纳入标准的不断发展和扩大。免疫检查点抑制剂（ICIs）在全身性HCC治疗中发挥了重要作用，并在肝移植前作为降分期/桥接治疗或作为LT后HCC复发的治疗中显示出潜力。然而,ICIs和免疫抑制药物之间的拮抗作用机制提出了重大挑战，特别是关于急性排斥反应（AR）的风险。本文分析了ICI治疗的主要信号通路，并总结了ICI治疗前后的研究现状。关于这一主题的文献有限且高度异质，排除明确的基于证据的结论。在LT之前使用ICI似乎很有希望，前提是实施了足够的清洗期。相比之下,LT后ICI治疗的结果不支持其广泛的临床应用,原因是AR发生率高且对治疗的总体反应较差.在未来,现代移植物保存技术可能支持选择良好的ICI响应者，但是迫切需要高水平研究的数据。
