Recent studies have revealed that besides the important role in triggering the adoptive antitumor immunity, dendritic cells (DCs) possess direct cytotoxic antitumor activity. Here, we investigated brain glioma patient monocyte-derived DCs generated in the presence of IFNα and GM-CSF (IFN-DCs). These DCs were characterized by reduced cytotoxic activity against TRAIL-resistant HEp-2 cells. The impairment of DC cytotoxic function was observed mainly in high-grade glioma patients and associated with poor survival. The dysfunction of patient DC cytotoxicity was partially restored under in vitro pretreatment of DCs with double-stranded human DNA as well as rIL-2. In contrast to healthy donors, IFN-DCs in a part of high-grade glioma patients also failed to lyse primary autologous or allogeneic glioma cells. Our findings point to possible contribution of DC impairment in tumor pathogenesis in brain glioma and justify the necessity to evaluate and correct DC cytotoxic function when exploring DCs as cancer vaccines in glioma.
Keywords: 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide; 7-AAD; 7-Aminoactinomycin D; CFSE; Cytotoxic activity; DCs; Dendritic cells; Double-stranded DNA; Glioma patients; IFNα; LPS; MTT; NK; TNF-related apoptosis-inducing ligand; TNFα; TRAIL; carboxyfluorescein succinimidyl ester; dendritic cells; double-stranded human DNA; dsDNA; interferon alpha; lipopolysaccharide; natural killer; rIL-2; recombinant interleukin 2; tumor necrosis factor alpha.
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