title: Effector gammadelta T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma.
abstract: The aim of this study was to investigate the in vitro immunomodulatory effects of zoledronic acid (Zol) on peripheral blood Vgamma9/Vdelta2 (gammadelta) T cells of normal donors and multiple myeloma (MM) patients. 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 gammadelta T cells was observed in 100% of normal donors and 50% of MM patients. gammadelta T cells produced IFN-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 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 gammadelta T cells and by enhancing the immunosensitivity of myeloma cells to gammadelta T cells. Mevastatin, a specific inhibitor of hydroxy-methylglutaryl-CoA reductase, completely abrogated this antimyeloma activity.
authors.affiliation: Laboratorio di Ematologia Oncologica, Centro di Ricerca in Medicina Sperimentale, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Mariani
authors.forename: M
authors.initials: M
authors.lastname: Muraro
authors.forename: F
authors.initials: F
authors.lastname: Pantaleoni
authors.forename: F
authors.initials: F
authors.lastname: Fiore
authors.forename: B
authors.initials: B
authors.lastname: Nuschak
authors.forename: S
authors.initials: S
authors.lastname: Peola
authors.forename: M
authors.initials: M
authors.lastname: Foglietta
authors.forename: A
authors.initials: A
authors.lastname: Palumbo
authors.forename: M
authors.initials: M
authors.lastname: Coscia
authors.forename: B
authors.initials: B
authors.lastname: Castella
authors.forename: B
authors.initials: B
authors.lastname: Bruno
authors.forename: R
authors.initials: R
authors.lastname: Bertieri
authors.forename: L
authors.initials: L
authors.lastname: Boano
authors.forename: M
authors.initials: M
authors.lastname: Boccadoro
authors.forename: M
authors.initials: M
authors.lastname: Massaia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007155:Immunologic Factors / Q000276:immunology; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D007155:Immunologic Factors; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid