Characterization of Circulating Dendritic Cells in Melanoma: Role of CCR6 in Plasmacytoid Dendritic Cell Recruitment to the Tumor
Characterization of Circulating Dendritic Cells in Melanoma: Role of CCR6 in Plasmacytoid Dendritic Cell Recruitment to the Tumor
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DOI：
10.1038/jid.2010.24
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发表时间：
2010-06-01
影响因子：
6.5
通讯作者：
Chaperot, Laurence
中科院分区：
文献类型：
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作者：
Charles, Julie;Di Domizio, Jeremy;Chaperot, Laurence
树突状细胞(DC)是产生抗肿瘤免疫反应的中心细胞，但在各种癌症中其数量和功能可能会发生变化。这些细胞在黑色素瘤的发展过程中是否受到影响尚不清楚。与对照组相比，我们研究了新诊断的黑色素瘤患者循环中髓系树突状细胞(MDCs)和浆细胞样树突状细胞(PDCs)的存在、表型和功能。与正常人相比，黑色素瘤患者PDCs和MDCs的频率相当。这两个循环DC亚群都是未成熟的，但在R848体外刺激下，它们有效地上调了它们的共刺激分子的表达。我们发现，来自黑色素瘤患者和对照组的循环DC显示出相似的趋化因子受体CXCR3、CXCR4、CCR7和CCR10的表达模式。值得注意的是，黑色素瘤患者的PDCs比对照组的PDCs表达更高水平的CCR6，并且能够向CCL20迁移。进一步的数据显示，CCR6表达的PDCs在黑色素瘤原发皮损中存在，CCL20在黑色素瘤肿瘤中产生。这些结果表明，在黑色素瘤患者确诊时，PDCs和MDCs具有功能，CCL20可能参与了它们从血液到肿瘤的募集。
Dendritic cells (DCs) are central cells in the development of antitumor immune responses, but the number and function of these cells can be altered in various cancers. Whether these cells are affected during the development of melanoma is not known. We investigated the presence, phenotype, and functionality of circulating myeloid DCs (MDCs) and plasmacytoid DCs (PDCs) in newly diagnosed melanoma patients, compared to controls. The frequencies of PDCs and MDCs were equivalent in melanoma patients as compared with normal subjects. Both circulating DC subsets were immature, but on ex vivo stimulation with R848 they efficiently upregulated their expression of costimulatory molecules. We found that circulating DCs from melanoma patients and controls displayed similar pattern of expression of the chemokine receptors CXCR3, CXCR4, CCR7, and CCR10. Strikingly, PDCs from melanoma patients expressed higher levels of CCR6 than control PDCs, and were able to migrate toward CCL20. Further data showed that CCR6-expressing PDCs were present in melanoma primary lesions, and that CCL20 was produced in melanoma tumors. These results suggest that PDCs and MDCs are functional in melanoma patients at the time of diagnosis, and that CCL20 may participate to their recruitment from the blood to the tumor.