Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand.
Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand.
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发表时间：
2000-06
期刊：
影响因子：
11.2
通讯作者：
Nicolas Mach;S. Gillessen;S. Wilson;Christine E. Sheehan;M. Mihm;G. Dranoff
中科院分区：
文献类型：
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作者：
Nicolas Mach;S. Gillessen;S. Wilson;Christine E. Sheehan;M. Mihm;G. Dranoff
粒细胞巨噬细胞集落刺激因子 (GM-CSF) 和 flt3 配体 (FL) 均可诱导树突状细胞 (DC) 的发育。为了比较这些细胞因子在体内刺激的 DC 的功能特性，我们使用逆转录病毒介导的基因转移来产生分泌高水平每种分子的鼠肿瘤细胞。注射表达 GM-CSF 或 FL 的肿瘤细胞导致脾脏和肿瘤浸润中 CD11c+ 细胞急剧增加。然而，与接种受辐射的、分泌 FL 的肿瘤细胞相比，接种受辐射的、分泌 GM-CSF 的肿瘤细胞可刺激更有效的抗肿瘤免疫。 GM-CSF 引发的卓越抗肿瘤免疫涉及广泛的 T 细胞细胞因子反应，而 FL 引发的有限 Th1 反应则相反。 GM-CSF 产生的 DC 是 CD8α-的，并且比 FL 产生的 DC 细胞表达更高水平的 B7-1 和 CD1d。转移性黑色素瘤患者的注射部位接种了经辐射的、经过改造、可分泌 GM-CSF 的自体肿瘤细胞，结果显示出类似的、表达高水平 B7-1 的密集 DC 浸润。这些发现揭示了 GM-CSF 和 FL 在增强体内 DC 功能方面的关键差异，并对肿瘤疫苗的制作具有重要意义。
Both granulocyte-macrophage colony-stimulating factor (GM-CSF) and flt3-ligand (FL) induce the development of dendritic cells (DCs). To compare the functional properties of DCs stimulated by these cytokines in vivo, we used retroviral-mediated gene transfer to generate murine tumor cells secreting high levels of each molecule. Injection of tumor cells expressing either GM-CSF or FL resulted in the dramatic increase of CD11c+ cells in the spleen and tumor infiltrate. However, vaccination with irradiated, GM-CSF-secreting tumor cells stimulated more potent antitumor immunity than vaccination with irradiated, FL-secreting tumor cells. The superior antitumor immunity elicited by GM-CSF involved a broad T cell cytokine response, in contrast to the limited Thl response elicited by FL. DCs generated by GM-CSF were CD8alpha- and expressed higher levels of B7-1 and CD1d than DCs cells generated by FL. Injection sites of metastatic melanoma patients vaccinated with irradiated, autologous tumor cells engineered to secrete GM-CSF demonstrated similar, dense infiltrates of DCs expressing high levels of B7-1. These findings reveal critical differences in the abilities of GM-CSF and FL to enhance the function of DCs in vivo and have important implications for the crafting of tumor vaccines.