Myeloid-derived suppressor cells inhibit T cell proliferation in human extranodal NK/T cell lymphoma: a novel prognostic indicator.
Myeloid-derived suppressor cells inhibit T cell proliferation in human extranodal NK/T cell lymphoma: a novel prognostic indicator.
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骨髓源性抑制细胞抑制人结外 NK/T 细胞淋巴瘤中的 T 细胞增殖：一种新的预后指标
DOI：
10.1007/s00262-015-1765-6
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Li J
中科院分区：
文献类型：
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作者：
Zhang H;Li ZL;Ye SB;Ouyang LY;Chen YS;He J;Huang HQ;Zeng YX;Zhang XS;Li J
骨髓源性抑制细胞（MDSC）的扩增及其与晚期疾病阶段的相关性已在实体癌中显示。本研究旨在探讨淋巴结NK/T细胞淋巴瘤（ENKL）中MDSCs的功能特点及其临床意义。通过流式细胞术分析，ENKL患者的循环HLA-DR− CD 33 + CD 11b + MDSC百分比高于健康对照组（P<0. 05，n = 32）。来自ENKL患者的这些MDSC（ENKL-MDSC）由CD 14+单核细胞（Mo-MDSC，> 60%）和CD 15+粒细胞（PMN-MDSC，<20%）MDSC组成。此外，与来自健康供体的MDSC的水平相比，这些ENKL-MDSC表达更高水平的Arg-1、iNOS和IL-17，并且它们表达中等水平的TGFβ和IL-10，但表达较低水平的CD 66 b。ENKL-MDSCs对抗CD 3抗体诱导的同种异体和自体CD 4 T细胞增殖有显著抑制作用（P< 0.05），但对CD 8 T细胞增殖仅有轻微抑制作用（P> 0.05）。有趣的是，ENKL-MDSC抑制IFNγ的分泌，但促进T细胞中IL-10、IL-17和TGFβ的分泌以及Foxp 3的表达。应用iNOS抑制剂、Arg-1和ROS可显著逆转CD 3诱导的MDSC对T细胞增殖的抑制作用（P< 0.05）。重要的是，基于多变量考克斯回归分析，HLA-DR− CD 33 + CD 11b+细胞和CD 14 + Mo-MDSC是无病生存期（DFS，P= 0.013和0.016）和总生存期（OS，P= 0.017和0.027）的独立预测因子。总体而言，我们的结果首次确定ENKL-MDSC（主要是Mo-MDSC）对患者具有预后价值，并对T细胞增殖具有抑制功能。
The expansion of myeloid-derived suppressor cells (MDSCs) and its correlation with advanced disease stage have been shown in solid cancers. Here, we investigated the functional features and clinical significance of MDSCs in extranodal NK/T cell lymphoma (ENKL). A higher percentage of circulating HLA-DR−CD33+CD11b+MDSCs was observed in ENKL patients than in healthy controls (P< 0.05,n= 32) by flow cytometry analysis. These MDSCs from ENKL patients (ENKL-MDSCs) consisted of CD14+monocytic (Mo-MDSCs, >60 %) and CD15+granulocytic (PMN-MDSCs, <20 %) MDSCs. Furthermore, these ENKL-MDSCs expressed higher levels of Arg-1, iNOS and IL-17 compared to the levels of MDSCs from healthy donors, and they expressed moderate levels of TGFβ and IL-10 but lower levels of CD66b. The ENKL-MDSCs strongly suppressed the anti-CD3-induced allogeneic and autologous CD4 T cell proliferation (P< 0.05), but they only slightly suppressed CD8 T cell proliferation (P> 0.05). Interestingly, ENKL-MDSCs inhibited the secretion of IFNγ but promoted IL-10, IL-17 and TGFβ secretion as well as Foxp3 expression in T cells. The administration of inhibitors of iNOS, Arg-1 and ROS significantly reversed the suppression of anti-CD3-induced T cell proliferation by MDSCs (P< 0.05). Importantly, based on multivariate Cox regression analysis, the HLA-DR−CD33+CD11b+cells and CD14+Mo-MDSCs were independent predictors for disease-free survival (DFS,P= 0.013 and 0.016) and overall survival (OS,P= 0.017 and 0.027). Overall, our results identified for the first time that ENKL-MDSCs (mainly Mo-MDSCs) have a prognostic value for patients and a suppressive function on T cell proliferation.