文章：

PD-1hiTIM-3+ T细胞与AML患者异基因干细胞移植后白血病复发相关并可预测复发

PD-1hiTIM-3+ T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation

原文发布日期：2015-07-31

DOI: 10.1038/bcj.2015.58

类型: Original Article

开放获取: 是

英文摘要：

Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1hiTIM-3+ cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1hiTIM-3+ T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing TN and TEMRA subsets. Importantly, increase of PD-1hiTIM-3+ cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation.

摘要翻译： 

异基因干细胞移植后白血病复发的预后较差，亟需有效的新疗法。T细胞通过移植物抗白血病效应在清除白血病过程中发挥关键作用，白血病复发被视为GVL效应失效的表现。T细胞耗竭是一种由程序性细胞死亡蛋白1（PD-1）和T细胞免疫球蛋白域与粘蛋白域3（TIM-3）等抑制分子介导的T细胞功能障碍状态。为评估T细胞耗竭及抑制通路是否参与异基因干细胞移植后白血病复发，我们对接受异基因移植的急性髓系白血病患者外周血T细胞进行了表型与功能研究。研究发现PD-1高TIM-3阳性细胞与移植后白血病复发密切相关。与耗竭状态一致，PD-1高TIM-3阳性T细胞存在功能缺陷，表现为白细胞介素2（IL-2）、肿瘤坏死因子-α（TNF-α）和γ干扰素（IFN-γ）分泌减少。此外，这些细胞通过丢失初始T细胞和终末分化效应记忆T细胞亚群，呈现出与耗竭性抗原经历T细胞一致的表型。重要的是，PD-1高TIM-3阳性细胞的增多出现在临床确诊白血病复发之前，提示其具有预测价值。本研究为移植后白血病复发提供了早期诊断方法和治疗靶点。

原文链接：

PD-1hiTIM-3+ T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation