Application of dendritic cells and neutrophil-derived TRAIL to cancer cell therapy in children

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1. Dendritic cell (DC) therapy in childhood cancer : Autologous DCs pulsed with tumor-specific peptides or tumor lysates were administered to patients with refractory/relapsed pediatric solid tumors. In one patient, the residual tumor disappeared following DC therapy and long-term remission was achieved. In other two patients, growth of the tumors was temporally suppressed for one or ten months. In these patients, an increase in number of CD8+HLA-DR+ lymphocytes and INF-γ+CD8+ lymphocytes were observed. DC-based immunotherapy may be feasible, well-tolerated and promising approach in the treatment of children with refractory malignant tumors.2. Gene expression in DCs : In order to elucidate the functional characteristics of DCs, difference in gene expression was examined between adult peripheral blood (APB)- and umbilical cord blood (UCB)-derived DCs. The expression of calgranulin, which is speculated to be related to the establishment of immunotolernce, and cell cycle-related genes was significantly higher in UCB-DCs than APB-DCs, while the Th1-related cytokine genes were expressed much higher in APB-DCs. In addition, the expression of inflammatory cytokine genes increased depending on the DC maturation. The results may suggest functional difference in immune reactivity between UCB- and APB-DCs.3. Anti-leukemic effect of neutrophil-derived TNF-related apoptosis-inducing ligand (TRAIL) : TRAIL was expressed in resting neutrophils at the mRNA and protein levels, and its expression was enhanced after stimulation with IFN-γ. Neutrophils expressed TRAIL on the cell surface and excrete it into the culture media. When Jurkat cells (leukemic cell line) were cultured with neutrophils in the presence of IFN-γ, the number of Jurkat cells undergoing apoptosis increased depending on the effector : target ratio. This cytotoxicity was suppressed partially by adding anti-TRAIL antibody to the media. The results suggest that neutrophils may exert their own antitumor effect by TRAIL.