Division of Transplantation Immunology & Mucosal Biology, King's College London, London, UK.
Department of Inflammation Biology, King's College London, London, UK.
Eur J Immunol. 2021 Oct;51(10):2373-2386. doi: 10.1002/eji.202048875. Epub 2021 Sep 4.
Liver transplantation is the ultimate treatment option for end-stage liver disease. Breakthroughs in surgical practice and immunosuppression have seen considerable advancements in survival after transplantation. However, the intricate management of immunosuppressive regimens, balancing desired immunological quiescence while minimizing toxicity has proven challenging. Diminishing improvements in long-term morbidity and mortality have been inextricably linked with the protracted use of these medications. As such, there is now enormous interest to devise protocols that will allow us to minimize or completely withdraw immunosuppressants after transplantation. Immunosuppression withdrawal trials have proved the reality of tolerance following liver transplantation, however, without intervention will only occur after several years at the risk of potential cumulative immunosuppression-related morbidity. Focus has now been directed at accelerating this phenomenon through tolerance-inducing strategies. In this regard, efforts have seen the use of regulatory cell immunotherapy. Here we focus particularly on regulatory T cells, discussing preclinical data that propagated several clinical trials of adoptive cell therapy in liver transplantation. Furthermore, we describe efforts to further optimize the specificity and survival of regulatory cell therapy guided by concurrent immunomonitoring studies and the development of novel technologies including chimeric antigen receptors and co-administration of low-dose IL-2.
肝移植是治疗终末期肝病的终极选择。手术实践和免疫抑制方面的突破使得移植后生存率有了显著提高。然而，免疫抑制方案的复杂管理，在最小化毒性的同时平衡所需的免疫静止状态，一直具有挑战性。长期发病率和死亡率的改善有限，与这些药物的长期使用密切相关。因此，现在人们非常有兴趣设计方案，以便在移植后能够最小化或完全停用免疫抑制剂。免疫抑制剂停药试验已经证明了肝移植后耐受的现实，但如果不进行干预，只有在几年后才会发生，存在潜在的累积免疫抑制相关发病率的风险。目前的重点已经转向通过诱导耐受的策略来加速这一现象。在这方面，人们已经努力使用调节性细胞免疫疗法。在这里，我们特别关注调节性 T 细胞，讨论了促进肝移植中过继细胞治疗的几项临床前数据。此外，我们还描述了通过同时进行免疫监测研究以及开发包括嵌合抗原受体和低剂量 IL-2 共同给药在内的新技术，进一步优化调节性细胞治疗的特异性和存活的努力。
