Exosomes bearing HLA-G are released by melanoma cells
Exosomes bearing HLA-G are released by melanoma cells
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DOI：
10.1016/j.humimm.2003.08.344
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发表时间：
2003-11-01
期刊：
影响因子：
2.7
通讯作者：
Rouas-Freiss, N
中科院分区：
文献类型：
--
作者：
Riteau, B;Faure, F;Rouas-Freiss, N
肿瘤细胞释放膜囊泡，称为外泌体，能够通过将肿瘤抗原转移到树突状细胞来特异性激活细胞毒性t淋巴细胞。相比之下，非经典人白细胞抗原(HLA)-G类I分子显示免疫耐受特性，可由肿瘤细胞异位表达，从而使其逃脱免疫监视。我们在这里描述了一个黑色素瘤细胞系，命名为Fon，从hla - g阳性黑色素瘤活检中建立，自发表达高水平的HLA-G1膜结合异构体。对Fon细胞释放的外泌体进行纯化，并用Western blotting和流式细胞术分析其在蔗糖梯度上的密度和蛋白质组成。值得注意的是，这些黑色素瘤来源的外泌体除了表达Lamp-2等已知的蛋白外，还含有HLA-G1。此外，转染HLA-G1 cDNA的hla - g阴性M8黑色素瘤细胞分泌含有HLA-G1的外泌体。因此，黑色素瘤源性外泌体上耐受原性HLA-G分子的存在可能为肿瘤调节宿主免疫反应提供了一种新的途径。中国生物医学工程学报，2003,(C)，中国生物医学工程学报，2003。Elsevier Inc.出版。
Tumor cells release membrane vesicles, named exosomes, capable of specific cytotoxic T-lymphocyte activation by transferring tumor antigens to dendritic cells. By contrast, the nonclassical human leucocyte antigen (HLA)-G class I molecule displays immunotolerant properties and can be ectopically expressed by tumor cells, thereby allowing their escape from immunosurveillance. We describe here that a melanoma cell line, named Fon, established from an HLA-G-positive melanoma biopsy, spontaneously expressed high levels of the HLA-G1 membrane-bound isoform. Exosomes released by Fon cells were purified and analyzed both for their density on sucrose gradient and their protein composition by Western bloting and flow cytometry. Besides the expression of well-described proteins such as Lamp-2, notably, these melanoma-derived exosomes bore HLA-G1. In addition, exosomes harboring HLA-G1 were secreted by the HLA-G-negative M8 melanoma cells transfected with the HLA-G1 cDNA. Thus, the presence of tolerogenic HLA-G molecules on melanoma-derived exosomes may provide a novel way for tumors to modulate host's immune response. Human Immunology 64, 1064-1072 (2003), (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Inc.