IL-6-stimulated CD11b+ CD14+ HLA-DR- myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus.
IL-6-stimulated CD11b+ CD14+ HLA-DR- myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus.
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DOI：
10.18632/oncotarget.2368
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发表时间：
2014-09-30
期刊：
影响因子：
--
通讯作者：
Lee KD
中科院分区：
文献类型：
--
作者：
Chen MF;Kuan FC;Yen TC;Lu MS;Lin PY;Chung YH;Chen WC;Lee KD
本研究的目的是评估髓源性抑制细胞（MDSCs）及其与IL-6在食管鳞状细胞癌（SCC）中的意义。我们检测了50例食管鳞状细胞癌患者和12例健康对照者外周血中CD11b+CD14+HLA-DR -髓样细胞的百分比和IL-6的水平。此外，我们通过在小鼠饮用水中添加4-硝基喹啉1-氧化物（4-NQO）诱导食管肿瘤，评估MDSC募集、IL-6水平与肿瘤进展的关系。本研究表明，与健康人群相比，食管SCC患者的循环CD11b+CD14+HLA-DR -细胞显著增加，这与临床分期、治疗反应和循环IL-6水平有关。在4- nqo诱导的食管肿瘤动物模型中，MDSC募集与侵袭性食管肿瘤及IL-6水平升高有关。IL-6刺激MDSCs中的活性氧、精氨酸酶1和p-STAT3。阻断IL-6可阻止MDSCs的诱导和4-NQO诱导的侵袭性肿瘤的发生。综上所述，MDSCs和IL-6水平可预测食管SCC患者的预后。此外，我们建议抑制IL-6作为治疗食管鳞状细胞癌的潜在策略。
The aim of this study was to assess the significance of myeloid-derived suppressor cells (MDSCs) and their association with IL-6 in esophageal squamous cell carcinoma (SCC). We examined the percentage of CD11b+CD14+HLA-DR− myeloid cells and the levels of IL-6 in the peripheral blood of 50 patients with esophageal SCC and 12 healthy controls. Moreover, we evaluated the relationship between MDSC recruitment, IL-6 levels, and tumor progression by adding 4-nitroquinoline 1-oxide (4-NQO) to the drinking water of mice to induce esophageal tumors. Here we demonstrated that circulating CD11b+CD14+HLA-DR− cells were significantly increased in esophageal SCC patients compared with healthy people, and this was associated with the clinical stage, treatment response and circulating IL-6 levels. In a 4-NQO-induced esophageal tumor animal model, MDSC recruitment was associated with invasive esophageal tumors and with increased IL-6 levels. IL-6 stimulated reactive oxygen species, arginase 1 and p-STAT3 in MDSCs. Blockade of IL-6 prevented induction of MDSCs and the incidence of 4-NQO- induced invasive tumors. In conclusion, the levels of MDSCs and IL-6 predicted the prognosis of patients with esophageal SCC. Moreover, we suggest inhibition of IL-6 as a potential strategy for the treatment of esophageal SCC.
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DOI：
10.4049/jimmunol.1000901
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lechner MG;Liebertz DJ;Epstein AL
通讯作者：
Epstein AL
影响因子：
--
作者：
Litzenburger UM;Opitz CA;Sahm F;Rauschenbach KJ;Trump S;Winter M;Ott M;Ochs K;Lutz C;Liu X;Anastasov N;Lehmann I;Höfer T;von Deimling A;Wick W;Platten M
通讯作者：
Platten M
影响因子：
4.4
作者：
Almand, B;Clark, JI;Gabrilovich, DI
通讯作者：
Gabrilovich, DI
影响因子：
45.3
作者：
Allum, William H.;Stenning, Sally P.;Langley, Ruth E.
通讯作者：
Langley, Ruth E.
影响因子：
11.2
作者：
Bunt, Stephanie K.;Yang, Linglin;Ostrand-Rosenberg, Suzanne
通讯作者：
Ostrand-Rosenberg, Suzanne