title: [Effect of zoledronate on the cytotoxicity of γδ T cells from PBMCs of osteosarcoma patients against osteosarcoma].
abstract: Objective  To investigate the effect of zoledronate (Zol) on the cytotoxicity of γδ T cells from peripheral blood mononuclear cells (PBMCs) of osteosarcoma (OS) patients against OS.   Methods  γδ T cells,  derived from PBMCs of patients with primary,  recurrent and metastatic OS,  were ex vivo expanded by Zol and IL-2. γδ T cell cytotoxicity against target cells was analyzed by a standard lactate dehydrogenase (LDH) release assay. IFN-γ secreted from γδ T cells was determined by ELISA kits. γδ T cells were incubated with different blocking Abs in order to investigate the mechanisms of recognition and killing of OS cells. Nude mice were inoculated with human OS cell line (HOS) by subcutaneous injection to create in vivo OS tumor models,  and received normal saline,  Zol,  γδ T cells,  or γδ T cells + Zol by tail vein injection,  respectively. The inhibition of tumor growth by the different methods was observed and compared.   Results  γδ T cells from PBMCs of patients with OS were selectively expanded by Zol+IL-2 in vitro,  and showed cytotoxicity against OS. In addition,  γδ T cells showed significantly higher cytotoxicity against OS cells after treatment with Zol,  and the mechanism of cytotoxicity was largely dependent on TCR pathway and perforin/plasmin pathway,  partly on TRAIL pathway and NKG2D pathway. Combination treatment of γδ T cells and Zol had stronger and longer-lasting inhibition on tumor growth in vivo,  compared with either drug alone.   Conclusion  Zol can promote γδ T cells' proliferation from PBMCs of OS patients and enhance γδ T cells' cytotoxicity against OS.
authors.affiliation: Department of Orthopaedics, Affiliated Hospital, Guilin Medical University, Guilin 541004, China. lzxpds@126.com
authors.forename: Zhaoxu
authors.initials: Z
authors.lastname: Li
authors.forename: Jicun
authors.initials: J
authors.lastname: Tang
authors.forename: Lingling
authors.initials: L
authors.lastname: Sun
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Ye
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001859:Bone Neoplasms / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D012516:Osteosarcoma / Q000276:immunology* / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid; D007371:Interferon-gamma