EBV Conference 2008 Guangzhou - Baylor College of Medicine

49 (RegID: 1883; 1884; 1885)
Pierre BUSSON
Institution: CNRS-Institut de Cancérologie Gustave Roussy
e-mail: pbusson@igr.fr
BLOOD DIFFUSION AND TH1-SUPPRESSIVE EFFECTS OF GALECTIN-9 CONTAINING
EXOSOMES RELEASED BY EPSTEIN-BARR VIRUS-INFECTED NASOPHARYNGEAL
CARCINOMA CELLS
Jihène Klibi 1, Toshiro Niki 2, Alexander Riedel3, Catherine Pioche-Durieu1, Mitsuomi Hirashima4, Fethi
Guemira 5, Sylvestre Le Moulec 6, Joël Guigay 1, Dinesh Adhikary3, Josef Mautner 3, Pierre
Busson 1
Oralabstract:
Although malignant cells from EBV-associated nasopharyngeal carcinoma consistently express several
immunogenic viral proteins, their strategy of immune escape has remained poorly understood so far. We
have previously reported that NPC cells express high levels of galectin 9 which is a ligand of the Tim3
receptor, a death-inducing receptor expressed by mature Th1 lymphocytes. In vitro studies have shown
that malignant NPC cells release exosomes containing galectin 9 in the extra-cellular medium
(Keryer-Bibens et al., BMC Cancer 2006). Subsequently, 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.
EBV Conference 2008 Guangzhou
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