肝内区域免疫对肝移植后肿瘤复发的影响
Role of Intrahepatic Regional Immunity in Post-Transplant Cancer Recurrence
肝脏恶性肿瘤是肝移植的一个主要适应症,但是肝移植后肿瘤复发却是影响受体长期生存的一个严峻临床挑战。肿瘤生物学特征、分期和移植后的免疫抑制状态一直被认为是肝癌复发的危险因素。而越来越多的证据表明,肝脏缺血再灌注(IR)对同种异体移植物的损伤则为肝移植后的肿瘤细胞侵袭性、转移性
提供了有利的免疫微环境。在活体肝移植中,边缘移植物(如小体积或脂肪移植物)的严重损伤与较低的无复发生存率之间的相关性,证实了IR 损伤与肿瘤复发之间的关联。IR 可引起肝内免疫微环境重构,包括恶化移植物损伤的促炎反应和加快组织修复的抗炎反应。然而,肝内区域免疫对移植后肿瘤复发的作
用尚不清晰。本文详述了IR 损伤诱导的肝内体液微环境和调节性区域免疫微环境,以及它们如何影响肝移植后肿瘤复发的最新研究进展。综合理解移植后肝内区域免疫,将为移植后肿瘤复发提供精准诊断、治疗和预后预测的新策略。
Hepatic malignancy is a major indication for liver transplantation; however, post-transplant cancer recurrence is an emerging clinical challenge affecting long-term outcomes. Pre-transplant tumor biology, staging, and post-transplant immunosuppression regimens have been elucidated as risk factors for recurrent liver cancer. However, increasing evidence indicates that hepatic ischemia and reperfusion (IR) injury to allografts are crucial to providing a favorable immunologic microenvironment for cancer cell invasiveness and metastasis after liver transplantation. The association of severe graft injury in marginal grafts, such as small-for-size or fatty grafts, with lower recurrence-free survival rates in living donor liver transplantations, substantiates the correlation between hepatic IR injury and cancer recurrence. IR have been demonstrated to trigger intrahepatic immunological microenvironment remodeling, including pro-inflammatory responses exacerbating graft injury and anti-inflammatory responses promoting tissue repair. However, the role of regional immunity in post-transplant cancer recurrence is not comprehensively understood. This review describes the up-to-date evidence of the intrahepatic humoral microenvironment and regional regulatory immunological microenvironment induced by IR injury, as well as their roles in cancer recurrence after liver transplantation. A comprehensive understanding of regional immunity will provide novel precise diagnostic, therapeutic, and prognostic strategies for post-transplant cancer recurrence.
Liver transplantation / Liver cancer / Recurrence / Immunology
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