Osteosarcoma cell line growth inhibition by zoledronate-stimulated effector cells

• Published in: Cellular immunology Vol. 249; no. 2; pp. 63 - 72
• Main Authors: Muraro, M., Mereuta, O.M., Carraro, F., Madon, E., Fagioli, F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-10-2007
• Subjects: Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Coculture Techniques; Cytotoxicity; Cytotoxicity Tests, Immunologic; Diphosphonates - pharmacology; Flow Cytometry; Gammadelta T cells; Humans; Imidazoles - pharmacology; Immunotherapy - methods; Osteosarcoma; Osteosarcoma - immunology; Receptors, Antigen, T-Cell, gamma-delta; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; Osteosarcoma; Cytotoxicity; Gammadelta T cells
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2007.11.005

Bisphosphonates have a profound effect on bone resorption and are widely used in the treatment of osteoclast-mediated bone diseases. Zoledronic acid (ZA), a third-generation biphosphonate, has a potent antitumor activity and expands gammadelta (γδ) T cells endowed of major histocompatibility complex-unrestricted lytic activity. Many solid tumors express tumor-specific antigens on their surface, representing targets for immune effector T cells. Nevertheless, the immune surveillance against clinically manifested tumors is relatively inefficient. Therefore, we investigated the hitherto unknown effects of ZA activated γδ T cells of normal donors on osteosarcoma cell lines. γδ T cells were stimulated with ZA and low doses of interleukin-2, and then analyzed for proliferation and generation of effector activity against osteosarcoma cell lines. Our results show the potent anti-tumor activity of ZA-stimulated γδ T cells and the enhanced immunosensitivity of osteosarcoma cell lines to γδ T cells suggesting that osteosarcoma is another γδ T cell susceptible tumor type.