MHC-mismatched mice liver transplantation promotes tumor growth in liver graft.
MHC-mismatched mice liver transplantation promotes tumor growth in liver graft.
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DOI：
10.1016/j.canlet.2014.05.010
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发表时间：
2014-08
期刊：
影响因子：
9.7
通讯作者：
Sheng Yan;Yuan Ding;Yang Tian;Zhongjie Lu;Yan Wang;Qiyi Zhang;Y. Ye;Lin Zhou;Haiyang Xie;Hui Chen;Ming H Zheng;Shusen Zheng
中科院分区：
文献类型：
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作者：
Sheng Yan;Yuan Ding;Yang Tian;Zhongjie Lu;Yan Wang;Qiyi Zhang;Y. Ye;Lin Zhou;Haiyang Xie;Hui Chen;Ming H Zheng;Shusen Zheng
肝移植是治疗肝脏恶性肿瘤的最终治疗选择，但手术后局部复发率仍然很高。然而，局部肿瘤复发的潜在机制仍然未知。我们推测移植肝的免疫状态可能有助于肿瘤的发展。将CT-26肿瘤细胞注射到异基因或同基因肝移植后的移植物中。分别于移植后3d、6d、9d、15 d观察移植肝内肿瘤的生长方式及调节性T细胞与效应性T细胞的相互关系。同种异体移植肝肿瘤替代面积明显大于同系移植肝。移植肝肿瘤的活化是由于移植肝中调节性T细胞介导的效应性T细胞功能失调所致。利用裸鼠移植模型，我们进一步证实了来自同种异体移植物的调节性T细胞在体内显著削弱效应性T细胞的功能。我们的数据表明，MHC不匹配的小鼠肝移植可以促进移植肝中的肿瘤生长。我们首次证明了肝移植物中肿瘤发展的易感性是由于调节性T细胞介导的效应T细胞功能的下调。
Liver transplantation is a final therapeutic option for treatment of hepatic malignancies, but local recurrence remains high after surgery. However, the underlying mechanisms of local tumor recurrence are still unknown. We speculated that immunological status of transplanted liver may contribute to the progress of tumor development. CT-26 tumor cells are injected into graft after allogeneic or syngeneic liver transplantation. The growth pattern of tumor and the co-relationship of regulatory T cell and effector T cells in liver graft were observed and investigated at 3d, 6d, 9d and 15d post-transplantation. The Hepatic Replacement Area of tumor in allogeneic grafts was significantly larger than that in syngeneic grafts. The activation of tumor growth in allografts was due to the dysfunction of effector T cells mediated by regulatory T cells in liver graft. Using nude mice model, we further confirmed that regulatory T cells from allograft significantly weaken the function of effector T cells in vivo. Our data has showed that MHC-mismatched mice liver transplantation can promote tumor growth in liver graft. For the first time, we demonstrated that susceptibility to tumor development in liver graft is due to the down-regulation of effector T cells’ function mediated by the regulatory T cells.