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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 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 Citation Map 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. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Blood diffusion and Th1-suppressive effects of galectin-9–containing exosomes released by Epstein-Barr virus–infected nasopharyngeal carcinoma cells Jihène Klibi1, Toshiro Niki2, Alexander Riedel3, Catherine Pioche-Durieu1, Sylvie Souquere4, Eric Rubinstein5, Sylvestre Le Moulec6, Joël Guigay7, Mitsuomi Hirashima8, Fethi Guemira9, Dinesh Adhikary3, Josef Mautner3, and Pierre Busson1 1 Université Paris-Sud, Centre National de la Recherche Scientifique (CNRS)–Unité Mixte de Recherche (UMR) 8126, Paris, France, and Institut de Cancérologie Gustave Roussy, Villejuif, France; 2 Gal Pharma, Kagawa, Japan; 3 Clinical Cooperation Group, Institute for Clinical and Molecular Biology, GSF-National Research Center for Environment and Health, Munich, Germany; 4 Unité Propre de Recherche (UPR) 1983 CNRS–Institut André Lwoff, Villejuif, France; 5 Inserm U602, Institut André Lwoff, Villejuif, France; 6 Adult Medicine Department, Institut de Cancérologie Gustave Roussy, Villejuif, France; 7 Cervicofacial Surgery and ENT Department, Institut de Cancérologie Gustave Roussy, Villejuif, France; 8 Department of Immunopathology, Faculty of Medicine, Kagawa University, Kagawa, Japan; and 9 Clinical Biology Department, Institut Salah Azaiz, Tunis, Tunisia 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 antigalectin-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 antitumoral 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]

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