Granulocytic myeloid-derived suppressor cells are cryosensitive and their frequency does not correlate with serum concentrations of colony-stimulating factors in head and neck cancer
Granulocytic myeloid-derived suppressor cells are cryosensitive and their frequency does not correlate with serum concentrations of colony-stimulating factors in head and neck cancer
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DOI：
10.1177/1753425912463618
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发表时间：
2013-06-01
期刊：
影响因子：
3.2
通讯作者：
Brandau, Sven
中科院分区：
文献类型：
--
作者：
Trellakis, Sokratis;Bruderek, Kirsten;Brandau, Sven
粒细胞髓源性抑制细胞（MDSC）是在各种癌症类型中扩增的MDSC亚群。由于许多临床研究依赖于使用储存的冷冻血液样本，我们首先测试了冷冻/解冻程序对粒细胞MDSC （G-MDSC）免疫表型和计数的影响。为了确定与人类G-MDSC扩增有关的因素，我们分析了头颈癌患者外周血中G-MDSC频率、临床参数和粒细胞相关因素之间的相关性。HLA-DR、CD14、CD33和CD66b可以明确区分G-MDSC与单核细胞MDSC和未成熟骨髓细胞。MDSC亚群对低温保存敏感，未成熟G-MDSC表现出最高的敏感性。G-MDSC频率在疾病晚期增加，与CCL4和CXCL8水平相关，但与集落刺激因子、IL-6、S100A8/9、CXCL1等细胞因子无关。我们的研究结果表明，在使用冷冻血液样本的回顾性临床分析中，MDSC的频率，特别是G-MDSC，可能被低估了。G-MDSC频率升高与疾病晚期和CXCL8浓度升高相关，但出乎意料的是，与生长因子（如粒细胞集落刺激因子）、IL-6和CXCL1无关。我们的数据表明，CXCL8在独立于传统集落刺激因子的情况下促进癌症患者G-MDSC的积累。
Granulocytic myeloid-derived suppressor cells (MDSC) are a MDSC subset expanded in various cancer types. As many clinical studies rely on the use of stored collections of frozen blood samples, we first tested the influence of freezing/thawing procedures on immunophenotyping and enumeration of granulocytic MDSC (G-MDSC). To identify factors involved in expansion of human G-MDSC, we then analyzed correlations between G-MDSC frequencies, clinical parameters and granulocyte-related factors in the peripheral blood of head and neck cancer patients. HLA-DR, CD14, CD33 and CD66b allowed a clear discrimination of G-MDSC from monocytic MDSC and immature myeloid cells. MDSC subsets were sensitive to cryopreservation with immature G-MDSC showing the highest sensitivity. G-MDSC frequencies were increased in advanced disease stage and associated with the level of CCL4 and CXCL8, but not with colony-stimulating factors, IL-6, S100A8/9, CXCL1 and other cytokines. Our results indicate that the frequency of MDSC, in particular G-MDSC, may be underestimated in retrospective clinical analyses using frozen blood samples. Increased G-MDSC frequencies correlate with advanced disease and increased concentrations of CXCL8, but, unexpectedly, not with growth factors (such as granulocyte colony-stimulating factor), IL-6 and CXCL1. Our data suggest that CXCL8 promotes accumulation of G-MDSC in cancer patients independent of classical colony-stimulating factors.