[HTML][HTML] Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects

DD Taylor, C Gercel-Taylor - British journal of cancer, 2005 - nature.com
DD Taylor, C Gercel-Taylor
British journal of cancer, 2005nature.com
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 …
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-ζ and JAK 3 expressions and induction of apoptosis, measured by DNA fragmentation.‘Exosome’components mediating suppression of CD3-ζ 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-ζ and JAK 3 and induced apoptosis. CD3-ζ 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.
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