Toll Like Receptor Agonists Enhance The Cytotoxity Of ?? T Cells Against Osteosarcoma Cells

Osteosarcoma is the most common primary osteogenic malignant tumor in childhood and adolescence with a prevalence of 3 cases per million people per year.The 5-year survival rate of osteosarcoma patient has improved to 60-70%due to combination of surgical resection and multi-agent chemotherapy,but hasn't been changed during last 3 decades.Additionally,the prognosis of the patient with recurrent or metastatic osteosarcoma is very poor,and current therapies have shown limited efficacy.OS remains the second highest cause of cancer-related death in children and adolescents.Therefore,the development of novel therapeutic strategies is urgent.?? T cells exert its anti-tumor effect and play an important role in immunotherapy of cancer.We have evaluated the sensitization of human osteosarcoma cells to y8 T-cell-mediated cytotoxicity by zoledronate.However,accumulating evidences demonstrate that inadequate capability of recognition to tumor cells and immunosuppressive tumor stroma cells like Tregs restrict the clinical application of ?? T cells.Following the conception of pattern recognition receptor,toll-like receptor possessing immunomodulatory effects makes great progress in immunology.This research program aims to explore the effect and mechanism of TLR agonists on cytotoxicity of ?? T cells to osteosarcoma cells in the presence of zoledronate or not,and interplay of ?? T cells with dendritic cells.These results will provide more evidences for the novel adoptive immunotherapy strategy.In this study,we first obtained the peripheral blood mononuclear cells from healthy volunteers.Then ?? T cells were expanded in the presence of ZOL and IL-2.Subsequently,we studied the effect of TLR3 ligand Poly(I:C)in ?? T cell sensitization.Here,we demonstrated that Poly(I:C)combined with y8T cells displayed a synergistic efficacy against OS cells.Moreover,our findings indicated that Poly(I:C)could increase CD54 expression on the surface of tumor cell and then induced the secretion of cytokine of y8T cells.Altogether,our study shows that Poly(I:C)could enhance ?? T cells anti-tummor efficacy against OS.