Archivio istituzionale della ricerca dell'Università degli Studi di Palermo
IRIS è il sistema di gestione integrata dei dati della ricerca (persone, pubblicazioni, progetti, attività) adottato dall’Università di Palermo, e ha lo scopo di raccogliere, conservare, documentare, e diffondere ad accesso aperto le informazioni relative alla produzione scientifica degli autori afferenti all’Ateneo.
EnglishImatinib 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.
D'Asaro, M., LA MENDOLA, C., DI LIBERTO, D., Orlando, V., Todaro, M., Spina, M., et al. (2010). V{gamma}9V{delta}2 T Lymphocytes Efficiently Recognize and Kill Zoledronate-Sensitized, Imatinib-Sensitive, and Imatinib-Resistant Chronic Myelogenous Leukemia Cells. JOURNAL OF IMMUNOLOGY, 184, 3260-3268 [10.4049/jimmunol.0903454].
| Data di pubblicazione: | 2010 | |
| Titolo: | V{gamma}9V{delta}2 T Lymphocytes Efficiently Recognize and Kill Zoledronate-Sensitized, Imatinib-Sensitive, and Imatinib-Resistant Chronic Myelogenous Leukemia Cells. | |
| Autori: | ||
| Citazione: | D'Asaro, M., LA MENDOLA, C., DI LIBERTO, D., Orlando, V., Todaro, M., Spina, M., et al. (2010). V{gamma}9V{delta}2 T Lymphocytes Efficiently Recognize and Kill Zoledronate-Sensitized, Imatinib-Sensitive, and Imatinib-Resistant Chronic Myelogenous Leukemia Cells. JOURNAL OF IMMUNOLOGY, 184, 3260-3268 [10.4049/jimmunol.0903454]. | |
| Rivista: | ||
| Digital Object Identifier (DOI): | http://dx.doi.org/10.4049/jimmunol.0903454 | |
| Abstract: | 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. | |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| D'Asaro et al 2010.pdf | N/A | Open Access Visualizza/Apri |
Copyright © 2021