Guan Xiaodong, Liu Zhiyu, Zhang Jianhua, Jin Xunbo
Shandong Provincial Hospital, Shandong University, Jinan, China.
Department of Urinary Surgery, Second Hospital of Dalian Medical University, Dalian, China.
Adv Clin Exp Med. 2018 Jul;27(7):947-953. doi: 10.17219/acem/70065.
Myeloid-derived suppressor cells (MDSC) play an important role in tumor-mediated immune evasion. Levels of MDSC in peripheral blood are increased in patients with cancer, correlating with cancer stage and outcome. Studies have confirmed the associations between MDSC and various cytokines in the peripheral blood of murine and human cancer hosts. However, little is known about the association between parenchymal MDSC subsets and cytokines, or the mechanism drawing MDSC into tumor parenchyma.
The aim of this study was to analyze the correlation between MDSC subsets and tumor grade as well as stage in renal cell carcinoma (RCC) patients. The expression of chemokine (C-C motif) ligand 2 (CCL2), interleukin 17 (IL-17) and interleukin 18 (IL-18) in the peripheral blood and parenchyma of RCC patients was also detected to explore its correlation with MDSC accumulation.
Total MDSC, granulocytic MDSC (G-MDSC), monocytic MDSC (M-MDSC), and immature MDSC (I-MDSC) from the blood and parenchyma were isolated and analyzed by flow cytometry. Cytokines were detected by the enzyme-linked immunosorbent assay (ELISA), real-time polymerase chain reaction (PCR) and western blot in blood and tumors.
Parenchymal levels of MDSC had a positive correlation with levels of CCL2, IL-17, and IL-18, suggesting these cytokines may attract MDSC into the parenchyma. Moreover, peripheral total MDSC, G-MDSC and I-MDSC were shown to correlate with tumor grade and stage. Gene and protein expression of CCL2, IL-17, and IL-18 was significantly increased in blood and tumors of RCC patients.
Our study has provided potential new targets for the risk stratification of patients with limited stages of renal carcinoma, in addition to elucidating a possible association between MDSC subsets and cytokine-induced migration into the tumor tissue.
髓系来源的抑制细胞（MDSC）在肿瘤介导的免疫逃逸中起重要作用。癌症患者外周血中MDSC水平升高，与癌症分期和预后相关。研究已证实小鼠和人类癌症宿主外周血中MDSC与多种细胞因子之间存在关联。然而，关于实质MDSC亚群与细胞因子之间的关联，或将MDSC吸引至肿瘤实质的机制，人们了解甚少。
本研究旨在分析肾细胞癌（RCC）患者中MDSC亚群与肿瘤分级及分期之间的相关性。还检测了RCC患者外周血和实质中趋化因子（C-C基序）配体2（CCL2）、白细胞介素17（IL-17）和白细胞介素18（IL-18）的表达，以探讨其与MDSC积聚的相关性。
通过流式细胞术分离并分析血液和实质中的总MDSC、粒细胞性MDSC（G-MDSC）、单核细胞性MDSC（M-MDSC）和未成熟MDSC（I-MDSC）。采用酶联免疫吸附测定（ELISA）、实时聚合酶链反应（PCR）和蛋白质印迹法检测血液和肿瘤中的细胞因子。
MDSC的实质水平与CCL2、IL-17和IL-18水平呈正相关，提示这些细胞因子可能将MDSC吸引至实质。此外，外周血中的总MDSC、G-MDSC和I-MDSC与肿瘤分级和分期相关。RCC患者血液和肿瘤中CCL2、IL-17和IL-18的基因和蛋白表达显著增加。
我们的研究除了阐明MDSC亚群与细胞因子诱导的向肿瘤组织迁移之间可能存在的关联外，还为局限性肾癌患者的风险分层提供了潜在的新靶点。
