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未受刺激的树突状细胞的基因表达谱可用作功能预测器。

The gene expression profile of unstimulated dendritic cells can be used as a predictor of function.

机构信息

Department of Oncology, Division of Clinical Sciences, St George's University of London, London, United Kingdom.

出版信息

Int J Cancer. 2012 Feb 15;130(4):979-90. doi: 10.1002/ijc.26101. Epub 2011 Jun 21.

Abstract

Dendritic cells (DCs) represent a subset of professional antigen presenting cell (APC) whose role is to elicit immune responses against harmful antigens. They have been used in DC vaccines to stimulate the immune system to kill cancer cells. However, successes in clinical trials have been limited, which may be attributed to a lack of appreciation of the quality of DCs used. In the present study, whole human genome microarrays were used to examine alterations in gene expression of monocyte-derived DCs after stimulation with supernatants derived from tumours. Our primary aim was to investigate the possibility of a gene signature for DCs that could be used to forecast responsiveness to tumour stimuli. Results showed that DCs are divided into two groups based on their ability to increase costimulatory markers and to trigger T-cell responses. The gene profiles of the immature DCs from these two groups were distinct, with particular divergence in genes from the interleukin (IL) 8 and thrombospondin-1 hubs. A subpanel of genes was identified, whose signature of expression was capable of predicting DC-stimulatory capacity. Overall, these studies have highlighted a gene-based screen that predicts DC function, which could be used to guide DC-vaccine trials.

摘要

树突状细胞(DCs)是一类专业的抗原呈递细胞(APC)亚群,其作用是引发针对有害抗原的免疫反应。它们已被用于 DC 疫苗中,以刺激免疫系统杀死癌细胞。然而,临床试验的成功有限,这可能归因于对所用 DC 质量的认识不足。在本研究中,使用全人类基因组微阵列来检测单核细胞来源的 DC 在受到肿瘤上清液刺激后的基因表达变化。我们的主要目的是研究是否存在可用于预测对肿瘤刺激反应性的 DC 基因特征。结果表明,根据增加共刺激标志物和触发 T 细胞反应的能力,DC 可分为两组。这两组不成熟 DC 的基因图谱明显不同,特别是白细胞介素(IL)8 和血小板反应蛋白-1 中心的基因明显不同。确定了一个亚群基因,其表达特征能够预测 DC 的刺激能力。总的来说,这些研究强调了一种基于基因的筛选方法,可以预测 DC 功能,从而指导 DC 疫苗试验。

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