Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2011;6(8):e22517. doi: 10.1371/journal.pone.0022517. Epub 2011 Aug 2.
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.
外泌体是由大多数细胞类型（包括肿瘤细胞）分泌的起源于内体的小膜囊泡。肿瘤来源的外泌体通常包含肿瘤抗原，并已被用作肿瘤抗原的来源，以刺激抗肿瘤免疫反应。然而，许多报道还表明，肿瘤来源的外泌体可以通过不同的机制促进肿瘤免疫逃逸，其中大多数机制与抗原无关。在本研究中，我们使用迟发型超敏反应（DTH）的小鼠模型，证明了局部给予携带模型抗原鸡卵清蛋白（OVA）的肿瘤来源的外泌体可特异性抑制 DTH 反应。对外泌体运输的分析表明，局部注射后，肿瘤来源的外泌体被 CD11c+细胞内化，并运送到引流淋巴结。外泌体介导的 DTH 抑制与引流淋巴结中 TGF-β1 和 IL-4 的 mRNA 水平升高有关。检查的肿瘤来源的外泌体也被发现抑制 DC 成熟。总之，我们的研究结果表明，肿瘤来源的外泌体可能通过调节 APC 的功能，在诱导肿瘤抗原特异性免疫抑制中发挥作用。
