Wolfers J, Lozier A, Raposo G, Regnault A, Théry C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T, Angevin E, Amigorena S, Zitvogel L
Immunology Unit, Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France.
Nat Med. 2001 Mar;7(3):297-303. doi: 10.1038/85438.
The initiation of T-cell-mediated antitumor immune responses requires the uptake and processing of tumor antigens by dendritic cells and their presentation on MHC-I molecules. Here we show in a human in vitro model system that exosomes, a population of small membrane vesicles secreted by living tumor cells, contain and transfer tumor antigens to dendritic cells. After mouse tumor exosome uptake, dendritic cells induce potent CD8+ T-cell-dependent antitumor effects on syngeneic and allogeneic established mouse tumors. Therefore, exosomes represent a novel source of tumor-rejection antigens for T-cell cross priming, relevant for immunointerventions.
T细胞介导的抗肿瘤免疫反应的启动需要树突状细胞摄取和处理肿瘤抗原,并将其呈递在MHC-I分子上。在此,我们在一个人类体外模型系统中表明,外泌体(一种由活肿瘤细胞分泌的小膜泡群体)含有肿瘤抗原并将其转移至树突状细胞。小鼠摄取肿瘤外泌体后,树突状细胞对同基因和异基因已建立的小鼠肿瘤诱导出强大的CD8+ T细胞依赖性抗肿瘤效应。因此,外泌体代表了一种用于T细胞交叉启动的新型肿瘤排斥抗原来源,与免疫干预相关。