Sensitization of human osteosarcoma cells to Vγ9Vδ2 T-cell-mediated cytotoxicity by zoledronate.
Despite improvements in the treatment of osteosarcoma, there is a need for new therapeutic strategies, in particular for the treatment of recurrent tumors and metastases. Adoptive immunotherapy with Vγ9Vδ2 T lymphocytes represents an attractive strategy. We have investigated combining adoptive immunotherapy with Vγ9Vδ2 T cells and zoledronate to optimize osteosarcoma therapy. Vγ9Vδ2 T cells, from healthy volunteers and patients with osteosarcoma, cultures alone demonstrated moderate or poor cytotoxic activity against osteosarcoma cell lines, respectively. The addition of zoledronate further increased cytotoxicity in vitro. This enhancement was largely dependent on the granule exocytose and partly on TRAIL pathways, was TCR-mediated and partly NKG2D-mediated. These data suggest that combined treatment of human osteosarcoma with zoledronate and Vγ9Vδ2 T cells may be an effective complement to current chemotherapies.
Department of Orthopaedics, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China.
Zhaoxu
Z
Li
Huiqin
H
Peng
Qiang
Q
Xu
Zhaoming
Z
Ye
D000293:Adolescent; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D002648:Child; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy* / Q000276:immunology; D054353:Perforin / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D055815:Young Adult; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D054353:Perforin; D000077211:Zoledronic Acid; D007371:Interferon-gamma