The Journal of Experimental Medicine
PBL InterferonSource
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 20 May 2002. doi:10.1084/jem.20011624
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Andreola, G.
Right arrow Articles by Fais, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Andreola, G.
Right arrow Articles by Fais, S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2002/5/1303/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 10, May 20, 2002 1303-1316
Induction of Lymphocyte Apoptosis by Tumor Cell Secretion of FasL-bearing Microvesicles

Giovanna Andreola1, Licia Rivoltini1, Chiara Castelli1, Veronica Huber1, Paola Perego2, Paola Deho1, Paola Squarcina1, Paola Accornero3, Francesco Lozupone4, Luana Lugini5, Annarita Stringaro5, Agnese Molinari5, Giuseppe Arancia5, Massimo Gentile6, Giorgio Parmiani1 and Stefano Fais4

1 Unit of Immunotherapy of Human Tumors, Istituto Nazionale dei Tumori, Milan 20133, Italy
2 Unit of Preclinical Chemotherapy and Pharmacology, Istituto Nazionale dei Tumori, Milan 20133, Italy
3 Unit of Immunotherapy and Gene Therapy, Istituto Nazionale dei Tumori, Milan 20133, Italy
4 Laboratory of Immunology, Istituto Superiore di Sanità, Rome 00161, Italy
5 Ultrastructures, Istituto Superiore di Sanità, Rome 00161, Italy
6 Virology Section, Department of Experimental Medicine and Pathology, University of Rome "La Sapienza", Rome 00161, Italy

Address correspondence to Licia Rivoltini, Unit of Immunotherapy of Human Tumors, Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. Phone: 39-02-2390-3245; Fax: 30-02-2390-2630; E-mail: rivoltini{at}istitutotumori.mi.it

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.

Key Words: melanoma • apoptosis • T cells • melanosome • microvesicles


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS