CXCL10/CXCR3 signaling mobilized-regulatory T cells promote liver tumor recurrence after transplantation
CXCL10/CXCR3 signaling mobilized-regulatory T cells promote liver tumor recurrence after transplantation
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DOI：
10.1016/j.jhep.2016.05.032
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发表时间：
2016-11-01
影响因子：
25.7
通讯作者：
Man, Kwan
中科院分区：
文献类型：
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作者：
Li, Chang Xian;Ling, Chang Chun;Man, Kwan
背景和目标：肝移植物损伤和肿瘤复发是肝细胞癌（HCC）患者肝移植的主要挑战。本研究旨在探讨肝移植损伤动员调节性T细胞（regulatory T cells，TCRs）在肝移植术后晚期肿瘤复发中的作用及机制。方法：采用大鼠原位肝移植模型和257例肝癌肝移植受者，研究TCRs动员与肿瘤复发、肝移植损伤的关系。在CXCL 10（-/-）和CXCR 3（-/-）小鼠肝脏IR损伤模型中研究CXCL 10/CXCR 3信号传导在TcB动员和肿瘤复发中的直接作用。GWR组患者外周血TGFs水平和移植物内TLR 4/CXCL 10/CXCR 3水平均高于GWR组
Background & Aims: Liver graft injury and tumor recurrence are the major challenges of liver transplantation for the patients with hepatocellular carcinoma (HCC). Here, we aimed to explore the role and mechanism of liver graft injury mobilizing regulatory T cells (Tregs), which lead to late phase tumor recurrence after liver transplantation.Methods: The correlation among tumor recurrence, liver graft injury and Tregs mobilization were studied in 257 liver transplant recipients with HCC and orthotopic rat liver transplantation models. The direct roles of CXCL10/CXCR3 signaling on Tregs mobilization and tumor recurrence were investigated in CXCL10(-/-) and CXCR3(-/-) mice models with hepatic IR injury.Results: Clinically, patients received the graft with graft weight ratio (GWR) = 60% graft. More circulating Tregs and higher intragraft TLR4/CXCL10/CXCR3 levels were detected in recipients with GWR