Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs)
Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs)
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DOI：
10.1158/1078-0432.ccr-15-2463
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发表时间：
2016-08-01
影响因子：
11.5
通讯作者：
Melero, Ignacio
中科院分区：
文献类型：
--
作者：
Alfaro, Carlos;Teijeira, Alvaro;Melero, Ignacio
目的：髓源性抑制细胞（MDSC）被认为是肿瘤患者T细胞免疫抑制的重要组成部分。吸引这些细胞到肿瘤微环境的因素知之甚少。IL 8（CXCL 8）是中性粒细胞和单核细胞的有效趋化因子。实验设计：MDSC通过Ficoll梯度分离的血液白细胞上的流式细胞术表征和分选，所述血液白细胞来自健康志愿者（n = 10）和晚期癌症患者（n = 28）。在趋化性测定中，测试分选的粒细胞和单核细胞MDSC对重组IL 8、源自癌细胞系的IL 8和患者血清的响应。共聚焦显微镜，荧光，和时间推移荧光共聚焦显微镜短期MDSC culture.Results：IL 8 chemoattracts粒细胞（GrMDSC）和单核细胞（MoMDSC）人MDSC的形成进行了评估。单核细胞而非粒细胞MDSC对从癌症患者循环中分离的自体T细胞的增殖具有抑制活性。IL 8没有改变人MDSC的T细胞抑制活性。然而，IL 8诱导的NET的形成在GrMDSC subset.Conclusions：IL 8来源于肿瘤有助于MDSC的趋化募集和功能控制。(C)2016年AACR。
Purpose: Myeloid-derived suppressor cells (MDSC) are considered an important T-cell immunosuppressive component in cancer-bearing hosts. The factors that attract these cells to the tumor microenvironment are poorly understood. IL8 (CXCL8) is a potent chemotactic factor for neutrophils and monocytes.Experimental Design: MDSC were characterized and sorted by multicolor flow cytometry on ficoll-gradient isolated blood leucokytes from healthy volunteers (n = 10) and advanced cancer patients (n = 28). In chemotaxis assays, sorted granulocytic and monocytic MDSC were tested in response to recombinant IL8, IL8 derived from cancer cell lines, and patient sera. Neutrophil extracellular traps (NETs) formation was assessed by confocal microscopy, fluorimetry, and time-lapse fluorescence confocal microscopy on short-term MDSC cultures.Results: IL8 chemoattracts both granulocytic (GrMDSC) and monocytic (MoMDSC) human MDSC. Monocytic but not granulocytic MDSC exerted a suppressor activity on the proliferation of autologous T cells isolated from the circulation of cancer patients. IL8 did not modify the T-cell suppressor activity of human MDSC. However, IL8 induced the formation of NETs in the GrMDSC subset.Conclusions: IL8 derived from tumors contributes to the chemotactic recruitment of MDSCand to their functional control. (C) 2016 AACR.