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Induction of Lymphocyte Apoptosis by Tumor Cell Secretion of FasL-bearing Microvesicles
The hypothesis that FasL expression by tumor cells may impair the in vivo efficacy of antitumor immune responses, through a mechanism known as ‘Fas tumor counterattack,’ has been recently questioned, becoming the object of an intense debate based on conflicting results. Here we definitely show that...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193755/ https://www.ncbi.nlm.nih.gov/pubmed/12021310 http://dx.doi.org/10.1084/jem.20011624 |
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author | Andreola, Giovanna Rivoltini, Licia Castelli, Chiara Huber, Veronica Perego, Paola Deho, Paola Squarcina, Paola Accornero, Paola Lozupone, Francesco Lugini, Luana Stringaro, Annarita Molinari, Agnese Arancia, Giuseppe Gentile, Massimo Parmiani, Giorgio Fais, Stefano |
author_facet | Andreola, Giovanna Rivoltini, Licia Castelli, Chiara Huber, Veronica Perego, Paola Deho, Paola Squarcina, Paola Accornero, Paola Lozupone, Francesco Lugini, Luana Stringaro, Annarita Molinari, Agnese Arancia, Giuseppe Gentile, Massimo Parmiani, Giorgio Fais, Stefano |
author_sort | Andreola, Giovanna |
collection | PubMed |
description | The hypothesis that FasL expression by tumor cells may impair the in vivo efficacy of antitumor immune responses, through a mechanism known as ‘Fas tumor counterattack,’ has been recently questioned, becoming the object of an intense debate based on conflicting results. Here we definitely show that FasL is indeed detectable in the cytoplasm of melanoma cells and its expression is confined to multivesicular bodies that contain melanosomes. In these structures FasL colocalizes with both melanosomal (i.e., gp100) and lysosomal (i.e., CD63) antigens. Isolated melanosomes express FasL, as detected by Western blot and cytofluorimetry, and they can exert Fas-mediated apoptosis in Jurkat cells. We additionally show that melanosome-containing multivesicular bodies degranulate extracellularly and release FasL-bearing microvesicles, that coexpress both gp100 and CD63 and retain their functional activity in triggering Fas-dependent apoptosis of lymphoid cells. Hence our data provide evidence for a novel mechanism potentially operating in Fas tumor counterattack through the secretion of subcellular particles expressing functional FasL. Such vesicles may form a sort of front line hindering lymphocytes and other immunocompetent cells from entering neoplastic lesions and exert their antitumor activity. |
format | Text |
id | pubmed-2193755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21937552008-04-14 Induction of Lymphocyte Apoptosis by Tumor Cell Secretion of FasL-bearing Microvesicles Andreola, Giovanna Rivoltini, Licia Castelli, Chiara Huber, Veronica Perego, Paola Deho, Paola Squarcina, Paola Accornero, Paola Lozupone, Francesco Lugini, Luana Stringaro, Annarita Molinari, Agnese Arancia, Giuseppe Gentile, Massimo Parmiani, Giorgio Fais, Stefano J Exp Med Article The hypothesis that FasL expression by tumor cells may impair the in vivo efficacy of antitumor immune responses, through a mechanism known as ‘Fas tumor counterattack,’ has been recently questioned, becoming the object of an intense debate based on conflicting results. Here we definitely show that FasL is indeed detectable in the cytoplasm of melanoma cells and its expression is confined to multivesicular bodies that contain melanosomes. In these structures FasL colocalizes with both melanosomal (i.e., gp100) and lysosomal (i.e., CD63) antigens. Isolated melanosomes express FasL, as detected by Western blot and cytofluorimetry, and they can exert Fas-mediated apoptosis in Jurkat cells. We additionally show that melanosome-containing multivesicular bodies degranulate extracellularly and release FasL-bearing microvesicles, that coexpress both gp100 and CD63 and retain their functional activity in triggering Fas-dependent apoptosis of lymphoid cells. Hence our data provide evidence for a novel mechanism potentially operating in Fas tumor counterattack through the secretion of subcellular particles expressing functional FasL. Such vesicles may form a sort of front line hindering lymphocytes and other immunocompetent cells from entering neoplastic lesions and exert their antitumor activity. The Rockefeller University Press 2002-05-20 /pmc/articles/PMC2193755/ /pubmed/12021310 http://dx.doi.org/10.1084/jem.20011624 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Andreola, Giovanna Rivoltini, Licia Castelli, Chiara Huber, Veronica Perego, Paola Deho, Paola Squarcina, Paola Accornero, Paola Lozupone, Francesco Lugini, Luana Stringaro, Annarita Molinari, Agnese Arancia, Giuseppe Gentile, Massimo Parmiani, Giorgio Fais, Stefano Induction of Lymphocyte Apoptosis by Tumor Cell Secretion of FasL-bearing Microvesicles |
title | Induction of Lymphocyte Apoptosis by Tumor Cell Secretion of FasL-bearing Microvesicles |
title_full | Induction of Lymphocyte Apoptosis by Tumor Cell Secretion of FasL-bearing Microvesicles |
title_fullStr | Induction of Lymphocyte Apoptosis by Tumor Cell Secretion of FasL-bearing Microvesicles |
title_full_unstemmed | Induction of Lymphocyte Apoptosis by Tumor Cell Secretion of FasL-bearing Microvesicles |
title_short | Induction of Lymphocyte Apoptosis by Tumor Cell Secretion of FasL-bearing Microvesicles |
title_sort | induction of lymphocyte apoptosis by tumor cell secretion of fasl-bearing microvesicles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193755/ https://www.ncbi.nlm.nih.gov/pubmed/12021310 http://dx.doi.org/10.1084/jem.20011624 |
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