首页> 美国卫生研究院文献>Cancer Science >Vascular endothelial growth factor (VEGF) impairs the motility and immune function of human mature dendritic cells through the VEGF receptor 2‐RhoA‐cofilin1 pathway
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Vascular endothelial growth factor (VEGF) impairs the motility and immune function of human mature dendritic cells through the VEGF receptor 2‐RhoA‐cofilin1 pathway

机译:血管内皮生长因子(VEGF)通过VEGF受体2-RhoA-cofilin1途径损害成熟树突状细胞的运动能力和免疫功能

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摘要

Dendritic cells (DCs) are potent and specialized antigen presenting cells, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses against cancer. Tumor cells can escape from immune attack by secreting suppressive cytokines that solely or cooperatively impair the immune function of DCs. However, the underlying mechanisms are not fully defined. Vascular endothelial growth factor (VEGF) has been identified as a major cytokine in the tumor microenvironment. To elucidate the effects of VEGF on the motility and immune function of mature DCs (mDCs), the cells were treated with 50 ng/mL VEGF and investigated by proteomics and molecular biological technologies. The results showed that VEGF can impair the migration capacity and immune function of mDCs through the RhoA‐cofilin1 pathway mediated by the VEGF receptor 2, suggesting impaired motility of mDCs by VEGF is one of the aspects of immune escape mechanisms of tumors. It is clinically important to understand the biological behavior of DCs and the immune escape mechanisms of tumor as well as how to improve the efficiency of antitumor therapy based on DCs.
机译:树突状细胞(DC)是有效的和专门的抗原呈递细胞,在引发和扩增针对癌症的先天性和适应性免疫反应中都起着至关重要的作用。肿瘤细胞可以通过分泌抑制性细胞因子而逃避免疫攻击,而这些抑制性细胞因子会单独或共同损害DC的免疫功能。但是,底层机制尚未完全定义。血管内皮生长因子(VEGF)已被确定为肿瘤微环境中的主要细胞因子。为了阐明VEGF对成熟DCs(mDCs)的运动性和免疫功能的影响,用50ng / mL VEGF处理细胞并通过蛋白质组学和分子生物学技术进行了研究。结果表明,VEGF可以通过VEGF受体2介导的RhoA-cofilin1途径损害mDC的迁移能力和免疫功能,提示VEGF破坏mDC的运动性是肿瘤免疫逃逸机制的方面之一。了解DC的生物学行为和肿瘤的免疫逃逸机制,以及如何提高基于DC的抗肿瘤治疗的效率在临床上具有重要意义。

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