Taïeb Julien, Chaput Nathalie, Zitvogel Laurence
ERIT-M 02-08 INSERM, Department of Clinical Biology, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France.
Crit Rev Immunol. 2005;25(3):215-23. doi: 10.1615/critrevimmunol.v25.i3.30.
Dendritic cells (DC) are professional antigen-presenting cells and the only ones capable of inducing primary cytotoxic immune responses both in vivo and in vitro. DCs secrete a 60-100 nm membrane vesicle population of endocytic origin, called exosomes. The lipid and protein composition of DC-derived exosomes (DEX) is now well characterized. Besides MHC and costimulatory molecules, DEX bear several adhesion proteins, which are probably involved in their specific targeting. DEX also accumulate several cytosolic factors, most likely involved in exosome's biogenesis in late endosomes. In 1998, we reported that DEX are immunogenic in mice and lead to tumor rejection. These findings have renewed the interest in DEX. The current challenge consists of understanding the mechanisms and the physiological relevance of DEX, which could contribute to the design of the optimal DEX-based vaccination. In this review, we focus on the biological features of DEX and their immunostimulatory functions in mice and humans, and we discuss their potential clinical implementation in the immunotherapy of cancer.
树突状细胞(DC)是专业的抗原呈递细胞,也是唯一能够在体内和体外诱导原发性细胞毒性免疫反应的细胞。DC分泌一种源自内吞作用的60 - 100纳米膜囊泡群体,称为外泌体。目前,DC来源的外泌体(DEX)的脂质和蛋白质组成已得到充分表征。除了主要组织相容性复合体(MHC)和共刺激分子外,DEX还带有几种粘附蛋白,它们可能参与了DEX的特异性靶向。DEX还积累了几种胞质因子,很可能参与了晚期内体中外泌体的生物发生。1998年,我们报道DEX在小鼠中具有免疫原性并能导致肿瘤排斥。这些发现重新引起了人们对DEX的兴趣。当前的挑战在于了解DEX的机制和生理相关性,这可能有助于设计基于DEX的最佳疫苗接种方案。在这篇综述中,我们重点关注DEX的生物学特性及其在小鼠和人类中的免疫刺激功能,并讨论它们在癌症免疫治疗中的潜在临床应用。