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.
Muraro
M
M
Stem Cell Transplantation and Cellular Therapy Unit, Regina Margherita Children's Hospital, Piazza Polonia 94, 10126 Turin, Italy. michela.muraro@unito.it
Mereuta
O M
OM
Carraro
F
F
Madon
E
E
Fagioli
F
F
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D004164:Diphosphonates / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods; D012516:Osteosarcoma / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology*; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid