Circulating CD14(+) HLA-DR(-/low) myeloid-derived suppressor cells in leukemia patients with allogeneic hematopoietic stem cell transplantation: novel clinical potential strategies for the prevention and cellular therapy of graft-versus-host disease.
Circulating CD14(+) HLA-DR(-/low) myeloid-derived suppressor cells in leukemia patients with allogeneic hematopoietic stem cell transplantation: novel clinical potential strategies for the prevention and cellular therapy of graft-versus-host disease.
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异基因造血干细胞移植白血病患者的循环CD14( )HLA-DR-/低骨髓源性抑制细胞：移植物抗宿主病预防和细胞治疗的新临床潜在策略
DOI：
10.1002/cam4.688
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发表时间：
2016-07
期刊：
影响因子：
4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Yin J;Wang C;Huang M;Mao X;Zhou J;Zhang Y
髓系抑制细胞(MDSCs)是一种异质性细胞群，包括未成熟的髓系细胞和巨噬细胞、树突状细胞(DC)、单核细胞和中性粒细胞的祖细胞。MDSCs在癌症患者和非癌症患者中的扩增和功能重要性已经被认识到。因此，人们越来越有兴趣了解它们在异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(AGVHD)中的作用。为了评估MDSCs在aGVHD发生和临床结局中的可能作用，本研究系统地检测了allo-HSCT后100天内MDSCs积聚的动态变化，并调查了MDSCs积聚过程中其他细胞类型和相关细胞因子的水平。结果表明，移植时MDSCs在移植物和外周血中的积聚可能有助于患者的整体免疫抑制，从而在不影响allo-HSCT后复发的情况下成功控制严重的aGVHD和长期存活。但移植物中的MDSCs水平具有更有利的预测能力。此外，在allo-HSCT后发生aGVHD的患者中，MDSCs比例显著增加。可能是由继发性炎症反应引起的，尤其与高浓度的IL-6和肿瘤坏死因子-α有关。但这种积累不能抵消aGVHD的恶化，也不会对临床结果和复发风险产生影响。总体而言，MDSCs可能被认为是治疗aGVHD的潜在新选择，并实现长期免疫耐受和存活。
Myeloid‐derived suppressor cells (MDSCs) are a heterogeneous cell population that includes immature myeloid cells and the progenitor cells of macrophages, dendritic cells (DCs), monocytes, and neutrophils. The expansion and functional importance of MDSCs in patients with cancer and noncancer pathogenic conditions has been recognized. As a result, there has been growing interest in understanding their roles in acute graft‐versus‐host disease (aGVHD) after allogenetic hematopoietic stem cell transplantation (allo‐HSCT). In order to evaluate possible effects of MDSCs on aGVHD development and clinical outcomes, this study systematically detected the dynamic changes of MDSCs accumulation in patients during the first 100 days after allo‐HSCT, and investigated the levels of other cell types and relative cytokines during MDSCs accumulation. Results showed that accumulation of MDSCs in the graft and in peripheral blood when engraftment might contribute to patients' overall immune suppression and result in the successful control of severe aGVHD and long‐term survival without influence on risk of recurrence after allo‐HSCT. But MDSCs levels in the graft had more favorable predictive abilities. Furthermore, MDSCs proportion significantly increased in patients developing aGVHD after allo‐HSCT. It might be caused by secondary inflammatory response, especially related to high concentrations of IL‐6 and TNF‐α. But this accumulation would not be able to counterbalance the aggravation of aGVHD and would not have influence on clinical outcomes and risk of relapse. Overall, MDSCs might be considered as potential new therapeutic option for aGVHD and achieve long‐term immunological tolerance and survival.