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Myeloma

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

Leukemia volume 19, pages 664–670 (2005)Cite this article

Abstract

The aim of this study was to investigate the in vitro immunomodulatory effects of zoledronic acid (Zol) on peripheral blood Vγ9/Vδ2 (γδ) T cells of normal donors and multiple myeloma (MM) patients. γδ 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 γδ T cells was observed in 100% of normal donors and 50% of MM patients. γδ T cells produced IFN-γ, 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 γδ 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 γδ T cells and by enhancing the immunosensitivity of myeloma cells to γδ T cells. Mevastatin, a specific inhibitor of hydroxy-methylglutaryl-CoA reductase, completely abrogated this antimyeloma activity.

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Acknowledgements

We would like to thank Professor John Iliffe for editorial assistance, and Dr Patrizia Falco, Dr Alessandra Bertola, and Dr Federica Cavallo for providing clinical samples. This work was supported by Compagnia San Paolo di Torino (Special Project Oncology), MIUR (COFIN and FIRB, Roma, Italy), AIRC (Milano, Italy), Ministero della Salute (Ricerca Sanitaria Finalizzata), and Novartis Pharma. Fellowship recipients are: S.P. (Comitato Gigi Ghirotti, Torino, Italy), M.M. (Associazione Italiana Amici José Carreras, Torino, Italy), and B.N. (CeRMS-FIRMS, Torino, Italy).

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Authors and Affiliations

  1. Laboratorio di Ematologia Oncologica, Centro di Ricerca in Medicina Sperimentale, Torino, Italy

    S Mariani, M Muraro, F Pantaleoni, F Fiore, B Nuschak, S Peola, M Foglietta, M Coscia, B Castella & M Massaia

  2. Dipartimento di Medicina ed Oncologia Sperimentale, Divisione di Ematologia dell'Università di Torino, Azienda, Ospedaliera, San Giovanni Battista, Torino, Italy

    F Fiore, M Foglietta, A Palumbo, B Bruno, M Boccadoro & M Massaia

  3. Novartis Pharma, Origgio, Italy

    R Bertieri & L Boano

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Correspondence to M Massaia.

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Mariani, S., Muraro, M., Pantaleoni, F. et al. Effector γδ T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma. Leukemia 19, 664–670 (2005). https://doi.org/10.1038/sj.leu.2403693

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