Cytomegalovirus-Specific T-Cell Transfer for Refractory Cytomegalovirus Infection After Haploidentical Stem Cell Transplantation: The Quantitative and Qualitative Immune Recovery for Cytomegalovirus
Cytomegalovirus-Specific T-Cell Transfer for Refractory Cytomegalovirus Infection After Haploidentical Stem Cell Transplantation: The Quantitative and Qualitative Immune Recovery for Cytomegalovirus
复制标题
单倍相合干细胞移植后巨细胞病毒特异性 T 细胞转移治疗难治性巨细胞病毒感染：巨细胞病毒的定量和定性免疫恢复
DOI：
10.1093/infdis/jix357
复制
发表时间：
2017-10-15
影响因子：
6.4
通讯作者：
Huang, Xiao-Jun
中科院分区：
文献类型：
--
作者：
Pei, Xu-Ying;Zhao, Xiang-Yu;Huang, Xiao-Jun
背景巨细胞病毒（CMV）特异性T细胞过继转移治疗单倍体相合干细胞移植（haplo-SCT）后难治性CMV感染的效率和机制仍不清楚。前瞻性入选了32例接受haplo-SCT后过继CMV特异性T细胞输注治疗的难治性CMV感染患者。另选取32例单倍体SCT后非难治性CMV感染患者作为对照组。在难治性队列和非难治性队列中，分析细胞治疗前后CMV特异性T细胞的表型和功能特征。在难治性队列中，32例接受治疗的患者中有27例在过继性T细胞转移后4周内表现出CMV清除，无复发。细胞治疗后观察到CMV特异性T细胞的体内扩增以及CMV特异性T细胞的细胞因子产生和增殖能力的改善。此外，观察到CMV特异性T细胞上程序性死亡-1（PD-1）的表达减少。然而，在其余5例CMV复发患者中，在转移后4周，CMV特异性T细胞的数量和功能均未恢复。CMV特异性T细胞的过继转移促进CMV特异性T细胞的数量和功能恢复，以防止单倍SCT后的难治性CMV感染。
Background. The efficiency and mechanisms of adoptive transfer of cytomegalovirus (CMV) specific T cells for refractory CMV infection after haploidentical stem cell transplantation (haplo-SCT) remain largely unknown.Methods. Thirty-two patients with refractory CMV infection who accepted treatment with adoptive CMV-specific T-cell infusion following haplo-SCT were prospectively enrolled. Another 32 patients with nonrefractory CMV infection after haplo-SCT were selected as control subjects. The phenotypical and functional characteristics of CMV-specific T cells were analyzed before and after cellular therapy in the refractory cohort, as well as in the nonrefractory cohort.Results. In the refractory cohort, 27 of the 32 treated patients exhibited CMV clearance within 4 weeks after adoptive T-cell transfer without recurrence. The in vivo expansion of CMV-specific T cells and improvements in the cytokine production and proliferation ability of the CMV-specific T cells were observed after cellular therapy. Moreover, a reduced expression of programmed death-1 (PD-1) on CMV-specific T cells was observed. However, in the remaining 5 patients who showed CMV recurrence 4 weeks after transfer, neither the quantity nor the function of CMV-specific T cells was restored.Conclusions. The adoptive transfer of CMV-specific T cells promotes quantitative and functional recovery of CMV-specific T cells to guard against refractory CMV infection after haplo-SCT.