Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein.
Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein.
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DOI：
10.1084/jem.20080132
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发表时间：
2008-09-29
期刊：
影响因子：
--
通讯作者：
Gabrilovich DI
中科院分区：
文献类型：
--
作者：
Cheng P;Corzo CA;Luetteke N;Yu B;Nagaraj S;Bui MM;Ortiz M;Nacken W;Sorg C;Vogl T;Roth J;Gabrilovich DI
与树突状细胞（DC）分化抑制相关的髓源性抑制细胞（MDSC）的积累是癌症中的主要免疫异常之一，并导致抗肿瘤免疫应答的抑制。这种现象的分子机制仍不清楚。我们在这里报告，STAT3诱导的骨髓相关蛋白S100A9的上调增强了癌症中MDSC的产生。缺乏这种蛋白质的小鼠产生了强有力的抗肿瘤免疫反应，并排斥植入的肿瘤。这种作用通过将来自荷瘤小鼠的野生型MDSC给予S100A9缺失小鼠而逆转。S100A9在体外培养的胚胎干细胞或转基因小鼠中的过表达抑制了DC和巨噬细胞的分化，并诱导了MDSC的积累。这项研究表明，肿瘤诱导的S100A9蛋白的上调对于MDSC的积累至关重要，并揭示了癌症免疫异常的新分子机制。
Accumulation of myeloid-derived suppressor cells (MDSCs) associated with inhibition of dendritic cell (DC) differentiation is one of the major immunological abnormalities in cancer and leads to suppression of antitumor immune responses. The molecular mechanism of this phenomenon remains unclear. We report here that STAT3-inducible up-regulation of the myeloid-related protein S100A9 enhances MDSC production in cancer. Mice lacking this protein mounted potent antitumor immune responses and rejected implanted tumors. This effect was reversed by administration of wild-type MDSCs from tumor-bearing mice to S100A9-null mice. Overexpression of S100A9 in cultured embryonic stem cells or transgenic mice inhibited the differentiation of DCs and macrophages and induced accumulation of MDSCs. This study demonstrates that tumor-induced up-regulation of S100A9 protein is critically important for accumulation of MDSCs and reveals a novel molecular mechanism of immunological abnormalities in cancer.
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DOI：
10.1046/j.1432-1033.2002.03002.x
发表时间：
2002-07-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Doussiere, J;Bouzidi, F;Vignais, PV
通讯作者：
Vignais, PV
影响因子：
4.4
作者：
Almand, B;Clark, JI;Gabrilovich, DI
通讯作者：
Gabrilovich, DI
影响因子：
4.8
作者：
Kerkhoff, C;Nacken, W;Doussiere, J
通讯作者：
Doussiere, J
影响因子：
4.4
作者：
Henkel, GW;McKercher, SR;Maki, RA
通讯作者：
Maki, RA
影响因子：
4.4
作者：
Cheng, PY;Zlobin, A;Gabrilovich, DI
通讯作者：
Gabrilovich, DI