Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells
Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells
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DOI：
10.1038/nm1201-1339
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发表时间：
2001-12-01
期刊：
影响因子：
82.9
通讯作者：
Curiel, TJ
中科院分区：
文献类型：
--
作者：
Zou, WP;Machelon, V;Curiel, TJ
肿瘤中树突状细胞（DQ）的运输和功能特征不佳，研究仅限于髓样DC（DC 1）。肿瘤抑制DC 1迁移和功能，可能阻碍特异性免疫。浆细胞样DC（DC 2）在肿瘤免疫中的作用尚不清楚。我们发现恶性人卵巢上皮性肿瘤细胞表达非常高水平的基质衍生因子-1，其诱导DC 2前体（preDC 2）趋化性和粘附/迁移，上调preDC 2极晚期抗原（VLA）-5，并通过CXC趋化因子受体-4保护preDC 2s免受肿瘤巨噬细胞白细胞介素-10诱导的凋亡。VLA-5配体血管细胞粘附分子-1介导preDC 2的粘附/传递。肿瘤前DC 2诱导显著的T细胞白细胞介素-10，与前DC 2分化或活化状态无关，这导致T细胞活化不良。未检测到髓样前体DC（preDC 1）。肿瘤可以通过吸引preDC 2并保护它们免受恶劣的微环境，以及通过改变preDC 1分布来削弱免疫力。
Dendritic-cell (DQ trafficking and function in tumors is poorly characterized, with studies confined to myeloid DCs (DC1s). Tumors inhibit DC1 migration and function, likely hindering specific immunity. The role of plasmacytoid DCs (DC2s) in tumor immunity is unknown. We show here that malignant human ovarian epithelial tumor cells express very: high levels of stromal-derived factor-1, which induces DC2 precursor (preDC2) chemotaxis and adhesion/transmigration, upregulates preDC2 very late antigen (VLA)-5, and protects preDC2s from tumor macrophage interleukin-10-induced apoptosis, all through CXC chemokine receptor-4. The VLA-5 ligand vascular-cell adhesion molecule-1 mediated preDC2 adhesion/transmig ration. Tumor preDC2s induced significant T-cell interleukin-10 unrelated to preDC2 differentiation or activation state, and this contributed to poor T-cell activation. Myeloid precursor DCs (preDC1s) were not detected. Tumors may weaken immunity by attracting preDC2s and protecting them from the harsh microenvironment, and by altering preDC1 distribution.