Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways
Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways
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DOI：
10.1016/j.bbrc.2005.06.065
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发表时间：
2005-08-19
影响因子：
3.1
通讯作者：
Mukhopadhyay, D
中科院分区：
文献类型：
--
作者：
Laxmanan, S;Robertson, SW;Mukhopadhyay, D
血管内皮生长因子（VEGF）是一种促血管生成的细胞因子，在肿瘤的生长和进展中起重要作用。最近的证据表明，一个替代的，虽然间接的，血管内皮生长因子对宿主免疫反应的肿瘤。VEGF似乎通过改变主要抗原呈递细胞如树突状细胞（DC）的功能来降低宿主免疫力[D. I. Gabrilovich，T.石田，S. Nadaf，J.E. Ohm，D. P. Carbone，血管内皮生长因子抗体通过改善内源性树突细胞功能增强癌症免疫治疗的功效，临床癌症研究5（1999）2963-2970，D.加布里洛维奇，T。石田T.奥马山，S. Ran，V. Kravtsov，S. Nadaf，D. P. Carbone，血管内皮生长因子抑制树突状细胞的发育并显著影响体内多种造血谱系的分化，Blood 92（1998）4150-4166，T.奥马山，S.兰，T。石田，S.纳达夫湖Kerr，D.P. Carbone，D.I. Gabrilovich，Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoictic progenitor cells，J.Immunol.160（1998）12241232.]。DC是宿主免疫的主要引发剂，因为已知它们激活初级和次级免疫应答[J. Banchereau，F.布里埃角Caux，J. Davoust，S. Lebecque，Y.J. Liu，B. Pulendran，K. Palucka，树突状细胞的免疫生物学，Ann.Rev.Immunol.18（2000）767-811.]。然而，VEGF如何抑制DC功能的确切性质尚不完全清楚。在这份报告中，我们表明，在VEGF的存在下培养的DC在刺激抗原特异性T细胞方面的效力较低。此外，通过使用来源于Flt-I信号传导缺陷的Idl（-/-）小鼠的DC，我们证明VEGF对DC功能的抑制功能最可能由Flt-I介导。因此，VEGF在下调宿主免疫中的作用可能突出VEGF在癌症发病机制中的独特作用。(c)2005年爱思唯尔公司All rights reserved.
Vascular endothelial growth factor (VEGF) is an angiogenic cytokine that plays an important role in tumor growth and progression. Recent evidence suggests an alternate, albeit indirect, role of VEGF on host immune response to tumors. VEGF appears to diminish host immunity by altering the function of major antigen-presenting cells such as dendritic cells (DCs) [D.I. Gabrilovich, T. Ishida, S. Nadaf, J.E. Ohm, D.P. Carbone, Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function, Clin. Cancer Res. 5 (1999) 2963-2970, D. Gabrilovich, T. Ishida, T. Oyama, S. Ran, V. Kravtsov, S. Nadaf, D.P. Carbone, Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo, Blood 92 (1998) 4150-4166, T. Oyama, S. Ran, T. Ishida, S. Nadaf, L. Kerr, D.P. Carbone, D.I. Gabrilovich, Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoictic progenitor cells, J. Immunol. 160 (1998) 12241232.]. DCs are prime initiators of host immunity as they are known to activate both primary as well as secondary immune responses [J. Banchereau, F. Briere, C. Caux, J. Davoust,S. Lebecque, Y.J. Liu, B. Pulendran, K. Palucka, Immunobiology of dendritic cells, Ann. Rev. Immunol. 18 (2000) 767-811.]. However, the exact nature of how VEGF suppresses DC function is not fully clear. In this report, we show that DCs cultured in the presence of VEGF are less potent in stimulating antigen-specific T-cells. Furthermore, by using DCs derived from Idl(-/-) mice that are defective in Flt-l signaling, we demonstrated that the inhibitory function of VEGF on DC function is most likely mediated by Flt-l. Thus, the role of VEGF in downregulating host immunity may highlight a unique role of VEGF in the pathogenesis of cancer. (c) 2005 Elsevier Inc. All rights reserved.