Altered maturation of peripheral blood dendritic cells in patients with breast cancer.
Altered maturation of peripheral blood dendritic cells in patients with breast cancer.
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DOI：
10.1038/sj.bjc.6601243
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发表时间：
2003-10-20
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
肿瘤至少有两种机制可以改变树突状细胞（DC）的成熟和功能。第一个影响造血祖细胞分化为功能性DC的能力;第二个影响它们从CD 14+单核细胞分化，促进早期但功能失调的成熟。本研究的目的是评估这些途径在乳腺癌患者体内的相关性。为此，将53名浸润性乳腺癌患者与68名健康对照者进行了比较。为了避免富集DC的分离或培养程序，直接通过流式细胞术对全血样品进行分析。评价LPS刺激后表面抗原的表达和调节性细胞因子的细胞内积累。肿瘤患者的DC数量，特别是髓系亚群的数量明显减少（P<0.001）。与对照组相比，患者DC的特征在于更成熟的表型（P=0.016），并且具有受损的IL-12产生（P<0.001）。这些改变通过手术切除肿瘤而恢复。为了研究某些肿瘤相关免疫活性可溶性因子的可能作用，我们测定了血管内皮生长因子、IL-10和精胺的血浆水平。精胺浓度与表达IL-12的DC百分比呈显著负相关，同时也发现精胺体外刺激单核细胞来源的DC可促进其活化和成熟，并损害其功能。两者合计，我们的研究结果表明，上述两种机制可以同时作用于乳腺癌，影响DC分化，精胺可能是一个介导的功能障碍的成熟的DC。
Tumours have at least two mechanisms that can alter dendritic cell (DC) maturation and function. The first affects the ability of haematopoietic progenitors to differentiate into functional DCs; the second affects their differentiation from CD14+ monocytes, promoting an early but dysfunctional maturation. The aim of this study was to evaluate the in vivo relevance of these pathways in breast cancer patients. For this purpose, 53 patients with invasive breast cancer were compared to 68 healthy controls. To avoid isolation or culture procedures for enrichment of DCs, analyses were directly performed by flow cytometry on whole-blood samples. The expression of surface antigens and intracellular accumulation of regulatory cytokines upon LPS stimulation were evaluated. The number of DCs, and in particular of the myeloid subpopulation, was markedly reduced in cancer patients (P<0.001). Patient DCs were characterized by a more mature phenotype compared with controls (P=0.016), and had impaired production of IL-12 (P<0.001). These alterations were reverted by surgical resection of the tumour. To investigate the possible role of some tumour-related immunoactive soluble factors, we measured the plasmatic levels of vascular endothelial growth factor, IL-10 and spermine. A significant inverse correlation between spermine concentration and the percentage of DCs expressing IL-12 was found. Evidence was also obtained that in vitro exposure of monocyte-derived DCs to spermine promoted their activation and maturation, and impaired their function. Taken together, our results suggest that both the above-described mechanisms could concomitantly act in breast cancer to affect DC differentiation, and that spermine could be a mediator of dysfunctional maturation of DCs.
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影响因子：
20.3
作者：
Dong, R;Cwynarski, K;Lombardi, G
通讯作者：
Lombardi, G
DOI：
10.1084/jem.190.10.1417
发表时间：
1999-11-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bell D;Chomarat P;Broyles D;Netto G;Harb GM;Lebecque S;Valladeau J;Davoust J;Palucka KA;Banchereau J
通讯作者：
Banchereau J
影响因子：
4.4
作者：
Harizi, H;Juzan, M;Gualde, N
通讯作者：
Gualde, N
DOI：
10.1093/jnci/89.3.245
发表时间：
1997-02-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Clerici, M;Merola, M;Clerici, E
通讯作者：
Clerici, E
影响因子：
8.4
作者：
CLERICI, M;FERRARIO, E;VILLA, ML
通讯作者：
VILLA, ML