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V{gamma}9V{delta}2 T Lymphocytes Efficiently Recognize and Kill Zoledronate-Sensitized, Imatinib-Sensitive, and Imatinib-Resistant Chronic Myelogenous Leukemia Cells.

  • Autori: D'Asaro, M.; LA MENDOLA, C.; DI LIBERTO, D.; Orlando, V.; Todaro, M.; Spina, M.; Guggino, G.; Meraviglia, S.; Caccamo, N.; Messina, A.; Salerno, A.; Di Raimondo, F.; Vigneri, P.; Stassi, G.; Fourniè, J.; Dieli, F.
  • Anno di pubblicazione: 2010
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • Parole Chiave: gamma delta T cells, Imatinib, Leukemia cells
  • OA Link:


Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20-30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pretreated with zoledronate. Vγ9Vδ2 T cell cytotoxicity was largely dependent on the granule exocytosis- and partly on TRAIL-mediated pathways, was TCR-mediated, and required isoprenoid biosynthesis by zoledronate-treated CML cells. Importantly, Vγ9Vδ2 T cells from patients with CML can be induced by zoledronate to develop antitumor activity against autologous and allogeneic zoledronate-treated leukemia cells, both in vitro and when transferred into immunodeficient mice in vivo. We conclude that intentional activation of Vγ9Vδ2 T cells by zoledronate may substantially increase their antileukemia activities and represent a novel strategy for CML immunotherapy.