De Stefano Nicola, Patrono Damiano, Colli Fabio, Rizza Giorgia, Paraluppi Gianluca, Romagnoli Renato
General Surgery 2U-Liver Transplant Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, University of Torino, Corso Bramante 88-90, 10126 Torino, Italy.
Cancers (Basel). 2024 Jun 28;16(13):2374. doi: 10.3390/cancers16132374.
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.
肝细胞癌（HCC）仍然是肝移植（LT）的主要肿瘤适应症，其纳入标准不断演变且范围不断扩大。免疫检查点抑制剂（ICIs）在HCC的全身治疗中发挥了核心作用，并在移植前作为降期/桥接治疗或作为LT后HCC复发的治疗方法在围移植期显示出潜力。然而，ICIs与免疫抑制药物之间的拮抗作用机制带来了重大挑战，尤其是在急性排斥反应（AR）风险方面。本综述分析了ICI疗法靶向的主要信号通路，并总结了LT前后ICI疗法的当前研究。关于该主题的文献有限且高度异质性，无法得出明确的循证结论。LT前使用ICIs似乎很有前景，但前提是要有足够的洗脱期。相比之下，LT后ICI治疗的结果不支持其广泛临床应用，因为AR发生率高且总体治疗反应不佳。未来，现代移植物保存技术可能有助于选择对ICI反应良好的患者，但迫切需要来自高级别研究的数据。
