Dendritic cells pulsed with heat-treated U251 cells induce antitumor immunity against malignant glioma

Abstract

Objective To investigate the ability and mechanism of dendritic cells (DCs) inducing specific cytotoxicity T cells to kill giloma cells.Methods DCs were induced and cultured from the murine bone marrow cells by using modified Inaba method in vitro.The biological characteristics of DCs were detected by an electron microscope and flow cytometry.The DCs vaccine was obtained by mixing DCs with apoptotic glioma cells induced by heating treatment.The capacity of DCs vaccine promoting proliferation and killing glioma cells was tested by the method of cell counting kit-8 (CCK-8).DCs vaccine was injected into the tumor-bearing mice via the tail vein to examine the tumor growth inhibition in vivo.Results The flow cytometry confirmed that DCs vaccine highly expressed the typical surface markers CD11C,CD80,CD86 and MHC Ⅱ,and that the optimal thermal condition for inducing apoptosis of glioma cells was 44 ℃for 3 h with the maximum apoptosis rate being (40.10 ± 1.08)％.DCs loaded with apoptotic glioma cells antigen could effectively promote T cell proliferation,and increase the interferon-γ (IFN-γ) secretion.And increased effector/target ratio enhanced the cytotoxity activity.Four weeks after vaccine treatment,tumor size was (301.704 ±21.659) mm3 in treatment group,and (487.116 ±65.975) mm3 in blank control group (P ＜0.01 ).Conclusion DCs,sensitized by heating treatment apoptotic glioma cells,can effectively promote T cell proliferation and induce specific cytotoxic T cells to kill glioma cellsin vitro,and inhibit tumor growth in vivo. Key words: Glioma; Dendritic cells; Tumor vaccine; Immunotherapy