| | |  | | | | Record from Web of Science® | | | | | | |
| Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects |
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| Author(s): Taylor DD, Gercel-Taylor C |
| Source: BRITISH JOURNAL OF CANCER Volume: 92 Issue: 2 Pages: 305-311 Published: JAN 31 2005 |
| Times Cited: 62 References: 44 |
| Abstract: Dendritic and lymphoid ' exosomes' regulate immune activation. Tumours release membranous material mimicking these ' exosomes,' resulting in deletion of reactive lymphocytes. Tumour- derived ' exosomes' have recently been explored as vaccines, without analysis of their immunologic consequences. This investigation examines the composition of tumour- derived ' exosomes' and their effects on T lymphocytes. Membranous materials were isolated from ascites of ovarian cancer patients ( n = 6) and Western immunoblotting was performed for markers associated with ' exosomes.' Using cultured T cells, ' exosomes' were evaluated for suppression of CD3-zeta and JAK 3 expressions and induction of apoptosis, measured by DNA fragmentation. ' Exosome' components mediating suppression of CD3-zeta were isolated by continuous eluting electrophoresis and examined by Western immunoblotting. ' Exosomes' were shown to be identical with previously characterised shed membrane vesicles by protein staining and TSG101 expression. ' Exosomes' expressed class I MHC, placental alkaline phosphatase, B23/ nucleophosmin, and FasL. ' Exosomes' suppressed expression of T- cell activation signalling components, CD3-zeta and JAK 3 and induced apoptosis. CD3-zeta suppression was mediated by two components: 26 and 42 kDa. Only the 42 kDa component reacted with anti- FasL antibody. These results indicate that, while ' exosomes' express tumour antigens, leading to their proposed utility as tumour vaccines, they also can suppress T- cell signalling molecules and induce apoptosis. |
| Document Type: Article |
| Language: English |
| Reprint Address: Taylor, DD (reprint author), Univ Louisville, Sch Med, Div Gynecol Oncol, Dept Obstet Gynecol & Womens Hlth, 511 S Floyd St,MDR 420, Louisville, KY 40202 USA |
Addresses:
1. Univ Louisville, Sch Med, Div Gynecol Oncol, Dept Obstet Gynecol & Womens Hlth, Louisville, KY 40202 USA
2. Univ Louisville, Sch Med, Dept Radiat Oncol, Louisville, KY 40202 USA |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Oncology |
| IDS Number: 890XF |
| ISSN: 0007-0920 |
| DOI: 10.1038/sj.bjc.6602316 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |