Osteosarcoma cell line growth inhibition by zoledronate-stimulated effector cells

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 (gammadelta) 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 gammadelta T cells of normal donors on osteosarcoma cell lines. gammadelta 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 gammadelta T cells and the enhanced immunosensitivity of osteosarcoma cell lines to gammadelta T cells suggesting that osteosarcoma is another gammadelta T cell susceptible tumor type.