Abstract
Exosomes, a type of membrane vesicles, released from tumor cells have been shown to be capable of transferring tumor antigens to dendritic cells and activating specific cytotoxic T-lymphocytes. Recent work has demonstrated the presence of high numbers of exosomes in malignant effusions. Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells and from which a significant number of dendritic cells can be produced. We hypothesized that the exosomes released from metastatic ovarian carcinoma were able to present tumor specific antigen to dendritic cells derived from unrelated umbilical cord blood, then could stimulate resting T cells to differentiate and induce effective cytotoxicity. Exosomes were isolated by ultracentrifugation of malignant ascites from ovarian cancer patients (n = 10). Purified exosomes were further characterized by Western blot analyses and immunoelectronic microscopy. Dendritic cells were collected from unrelated umbilical cord blood and cultured in the presence of GM-CSF, IL-4 and TNF-α. Resting T cells were mixed with dentritic cells previously primed with exosomes and the cytotoxicity were measured by MTT method. T cells were activated by DCs presented with exosomes. 1) the exosomes isolated from the ascites were membrane vesicles of about 30-90nm in diameter; 2) the exosomes expressed MHC class I molecules, HSP70, HSP90, Her2/Neu, and Mart1; and 3)umbilical cord blood-derived DCs previously exosome-primed stimulated resting T cells to differentiate and produce effective cytotoxicity. These results suggested that tumor-specific antigens present on exosomes can be presented by DCs derived from unrelated umbilical cord blood to induce tumor specific cytotoxicity and this may represent as a novel immunotherapy for ovarian cancer.
Highlights
Exosomes are small membrane vesicles secreted into the extracellular compartment by exocytosis
1) the exosomes isolated from the ascites were membrane vesicles of about 30–90nm in diameter; 2) the exosomes expressed MHC class I molecules, HSP70, HSP90, Her2/Neu, and Mart1; and 3)umbilical cord blood-derived DCs previously exosome-primed stimulated resting T cells to differentiate and produce effective cytotoxicity. These results suggested that tumor-specific antigens present on exosomes can be presented by DCs derived from unrelated umbilical cord blood to induce tumor specific cytotoxicity and this may represent as a novel immunotherapy for ovarian cancer
Recent work suggested that tumor derived-exosomes are immunogenic [5] and exosomes may be a novel source of tumor-specific antigens which may be used for T-cell cross priming and be relevant for immuno-interventions
Summary
Exosomes are small membrane vesicles secreted into the extracellular compartment by exocytosis. These subcellular membrane vesicles from endosomal origin are secreted upon fusion of multi-vesicular bodies with the plasma membrane [1, 2]. Exosomes have a “cellular” membrane oriented with a limited variety of proteins derived from the cytosol, endocytic compartment membranes, and plasma membranes [3]. They are 30 to 90 nm in diameter, and may be involved in the communication between cells. Recent work suggested that tumor derived-exosomes are immunogenic [5] and exosomes may be a novel source of tumor-specific antigens which may be used for T-cell cross priming and be relevant for immuno-interventions
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