Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects.
Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects.
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DOI：
10.1038/sj.bjc.6602316
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发表时间：
2005-01-31
影响因子：
8.8
通讯作者：
Gerçel-Taylor, C
中科院分区：
文献类型：
--
作者：
Taylor, DD;Gerçel-Taylor, C
树突状细胞和淋巴组织的‘外切体’调节免疫激活。肿瘤释放出类似于这些‘外切体’的膜性物质，导致反应性淋巴细胞的缺失。肿瘤衍生的‘外切体’最近被作为疫苗进行了探索，但没有分析它们的免疫学后果。这项研究考察了肿瘤来源的‘外切体’的组成及其对T淋巴细胞的影响。从卵巢癌患者(n=6)的腹水中分离出膜性物质，并进行免疫印迹以检测与‘外切体’相关的标记。利用培养的T细胞，通过DNA片段化的方法，评估了‘Exosome’抑制CD3-ζ和JAK3的表达和诱导细胞凋亡。用连续洗脱电泳法分离抑制CD3-ζ的‘外体’组分，并用免疫印迹法检测。通过蛋白质染色和TSG101的表达，表明‘Exosome’与先前描述的脱落膜小泡相同。‘Exosome’表达I类MHC、胎盘碱性磷酸酶、B23/核磷蛋白和FasL。‘Exosome’抑制T细胞激活信号成分CD3-ζ和JAK3的表达，并诱导细胞凋亡。CD3-ζ的抑制由两个组分介导：26和42 kDa。仅有42kDa组分与抗 抗体反应。这些结果表明，虽然‘外切体’表达肿瘤抗原，导致它们被认为是肿瘤疫苗，但它们也可以抑制T细胞信号分子和诱导细胞凋亡。
Dendritic and lymphoid ‘exosomes’ regulate immune activation. Tumours release membranous material mimicking these ‘exosomes,’ resulting in deletion of reactive lymphocytes. Tumour-derived ‘exosomes’ have recently been explored as vaccines, without analysis of their immunologic consequences. This investigation examines the composition of tumour-derived ‘exosomes’ and their effects on T lymphocytes. Membranous materials were isolated from ascites of ovarian cancer patients (n=6) and Western immunoblotting was performed for markers associated with ‘exosomes.’ Using cultured T cells, ‘exosomes’ were evaluated for suppression of CD3-ζ and JAK 3 expressions and induction of apoptosis, measured by DNA fragmentation. ‘Exosome’ components mediating suppression of CD3-ζ were isolated by continuous eluting electrophoresis and examined by Western immunoblotting. ‘Exosomes’ were shown to be identical with previously characterised shed membrane vesicles by protein staining and TSG101 expression. ‘Exosomes’ expressed class I MHC, placental alkaline phosphatase, B23/nucleophosmin, and FasL. ‘Exosomes’ suppressed expression of T-cell activation signalling components, CD3-ζ and JAK 3 and induced apoptosis. CD3-ζ suppression was mediated by two components: 26 and 42 kDa. Only the 42 kDa component reacted with anti-FasL antibody. These results indicate that, while ‘exosomes’ express tumour antigens, leading to their proposed utility as tumour vaccines, they also can suppress T-cell signalling molecules and induce apoptosis.
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影响因子：
5.8
作者：
Chaput, N;Taïeb, J;Zitvogel, L
通讯作者：
Zitvogel, L
影响因子：
4.7
作者：
Gibb, RK;Taylor, DD;GercelTaylor, C
通讯作者：
GercelTaylor, C
影响因子：
5.5
作者：
André, F;Scharz, NEC;Zitvogel, L
通讯作者：
Zitvogel, L
DOI：
10.1083/jcb.101.3.942
发表时间：
1985-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Pan BT;Teng K;Wu C;Adam M;Johnstone RM
通讯作者：
Johnstone RM
影响因子：
3.4
作者：
Gercel-Taylor, C;O'Connor, SM;Taylor, DD
通讯作者：
Taylor, DD