SEARCH:   Advanced

Blood, 26 February 2009, Vol. 113, No. 9, pp. 1957-1966. Prepublished online as a Blood First Edition Paper on November 12, 2008; DOI 10.1182/blood-2008-02-142596. This Article Full Text (PDF) Supplemental Tables and Figures Erratum (v114,p3974) All Versions of this Article: blood-2008-02-142596v1 113/9/1957    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Klibi, J. Articles by Busson, P. Search for Related Content PubMed PubMed Citation Articles by Klibi, J. Articles by Busson, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 28, 2008 Accepted October 28, 2008 Blood diffusion and Th1-suppressive effects of galectin-9-containing exosomes released by Epstein-Barr virus-infected nasopharyngeal carcinoma cells Jihene Klibi, Toshiro Niki, Alexander Riedel, Catherine Pioche-Durieu, Sylvie Souquere, Eric Rubinstein, Sylvestre Le Moulec, Joel Guigay, Mitsuomi Hirashima, Fethi Guemira, Dinesh Adhikary, Josef Mautner, and Pierre Busson* Universite Paris-Sud, CNRS UMR 8126, Institut de Cancerologie Gustave Roussy, Villejuif, France Gal Pharma, Takamatsu, Kagawa, Japan Clinical Cooperation Group, Institute for Clinical and Molecular Biology, GSF, Munich, Germany UPR 1983 CNRS-Institut Andre Lwoff, Villejuif, France INSERM U 602, Institut Andre Lwoff, Villejuif, France Adult Medicine Department, Institut de Cancerologie Gustave Roussy, Villejuif, France Cervicofacial Surgery and ENT Department, Institut de Cancerologie Gustave Roussy, Villejuif, France Department of Immunopathology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa, Japan Clinical Biology Department, Institut Salah Azaiz, Tunis, Tunisia * Corresponding author; email: pbusson{at}igr.fr. Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is the third most frequent virus-associated human malignancy. How this tumor escapes immune recognition despite the expression of several viral antigens has remained poorly understood. Our previous in vitro studies have shown that NPC cells release exosomes containing high amounts of galectin-9, a ligand of the membrane receptor Tim-3, which is able to induce apoptosis in mature Th1 lymphocytes. Here, we sought to determine whether galectin-9-carrying exosomes were produced in NPC patients and whether such exosomes might play a role in the immune evasion of NPC cells. We report that galectin-9-containing exosomes are selectively detected in plasma samples from NPC patients and mice xenografted with NPC tumors. The incorporation into exosomes protects galectin-9 against proteolytic cleavage but retains its Tim-3-binding capacity. Importantly, NPC exosomes induce massive apoptosis in EBV-specific CD4+ cells used as a model of target T cells. This effect is inhibited by both anti-Tim-3 and anti-galectin-9 blocking antibodies. These results indicate that blocking galectin-9/Tim-3 interaction in vivo might alleviate the Th1 suppressive effect of NPC exosomes and sustain anti-tumoral T cell responses, and thereby improve clinical efficacy of immunotherapeutic approaches against NPC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Smith, L. Beagley, and R. Khanna Acquisition of Polyfunctionality by Epstein-Barr Virus-Specific CD8+ T Cells Correlates with Increased Resistance to Galectin-1-Mediated Suppression J. Virol., June 15, 2009; 83(12): 6192 - 6198. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020