Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.
Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.
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DOI：
10.1371/journal.pone.0022517
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Robbins PD
中科院分区：
文献类型：
--
作者：
Yang C;Kim SH;Bianco NR;Robbins PD
外泌体是内体来源的小膜囊泡，其由包括肿瘤细胞在内的大多数细胞类型分泌。肿瘤来源的外泌体通常含有肿瘤抗原，并已被用作肿瘤抗原的来源以刺激抗肿瘤免疫应答。然而，许多报道也表明，肿瘤来源的外泌体可以通过不同的机制促进肿瘤免疫逃避，其中大多数是抗原非依赖性的。在本研究中，我们使用了迟发型超敏反应（DTH）的小鼠模型，并证明了携带模型抗原鸡卵清蛋白（OVA）的肿瘤来源的外泌体的局部给药导致以抗原特异性方式抑制DTH反应。外泌体运输的分析表明，局部注射后，肿瘤来源的外泌体被CD 11 c+细胞内化并运输到引流LN。外泌体介导的DTH抑制与引流LN中TGF-β1和IL-4的mRNA水平增加相关。还发现检查的肿瘤来源的外泌体抑制DC成熟。总之，我们的结果表明肿瘤来源的外泌体在诱导肿瘤抗原特异性免疫抑制中的作用，可能是通过调节APC的功能。
Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH) and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA) resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs.
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DOI：
10.1038/mt.2008.1
发表时间：
2008-04
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
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作者：
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影响因子：
12.4
作者：
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作者：
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