The aim of this study was to investigate the in vitro immunomodulatory effects of zoledronic acid (Zol) on peripheral blood Vitalic gamma9/Vdelta2 (italic gammadelta) T cells of normal donors and multiple myeloma (MM) patients. italic gammadelta T cells were stimulated with Zol and low doses of interleukin-2 (IL-2), and then analyzed for proliferation, cytokine production, and generation of effector activity against myeloma cell lines and primary myeloma cells. Proliferation of italic gammadelta T cells was observed in 100% of normal donors and 50% of MM patients. italic gammadelta T cells produced IFN-italic gamma, surface mobilized the CD107a and CD107b antigens, and exerted direct cell-to-cell antimyeloma activity irrespective of the ability to proliferate to Zol and IL-2. The memory phenotype was predominant in the MM italic gammadelta T cells that proliferated in response to Zol (responders), whereas effector cells were predominant in those that did not (nonresponders). Zol induced antimyeloma activity through the monocyte-dependent activation of italic gammadelta T cells and by enhancing the immunosensitivity of myeloma cells to italic gammadelta T cells. Mevastatin, a specific inhibitor of hydroxy-methylglutaryl-CoA reductase, completely abrogated this antimyeloma activity.

Effector gammadelta T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma

MARIANI, Sara;Peola S;FOGLIETTA, MYRIAM;PALUMBO, Antonio;COSCIA, Marta;CASTELLA, BARBARA;BRUNO, Benedetto;BOCCADORO, Mario;MASSAIA, Massimo
2005-01-01

Abstract

The aim of this study was to investigate the in vitro immunomodulatory effects of zoledronic acid (Zol) on peripheral blood Vitalic gamma9/Vdelta2 (italic gammadelta) T cells of normal donors and multiple myeloma (MM) patients. italic gammadelta T cells were stimulated with Zol and low doses of interleukin-2 (IL-2), and then analyzed for proliferation, cytokine production, and generation of effector activity against myeloma cell lines and primary myeloma cells. Proliferation of italic gammadelta T cells was observed in 100% of normal donors and 50% of MM patients. italic gammadelta T cells produced IFN-italic gamma, surface mobilized the CD107a and CD107b antigens, and exerted direct cell-to-cell antimyeloma activity irrespective of the ability to proliferate to Zol and IL-2. The memory phenotype was predominant in the MM italic gammadelta T cells that proliferated in response to Zol (responders), whereas effector cells were predominant in those that did not (nonresponders). Zol induced antimyeloma activity through the monocyte-dependent activation of italic gammadelta T cells and by enhancing the immunosensitivity of myeloma cells to italic gammadelta T cells. Mevastatin, a specific inhibitor of hydroxy-methylglutaryl-CoA reductase, completely abrogated this antimyeloma activity.
2005
19 (4)
664
670
Mariani S; Muraro M; Pantaleoni F; Fiore F; Nuschak B; Peola S; Foglietta M; Palumbo A; Coscia M; Castella B; Bruno B; Bertieri R; Boano L; Boccadoro M; Massaia M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/41373
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