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

1.树突状细胞（DC）治疗儿童癌症：将肿瘤特异性肽或肿瘤裂解物脉冲的Autumn DC给予难治性/复发性儿科实体瘤患者。在一名患者中，残留肿瘤在DC治疗后消失，并实现了长期缓解。另2例肿瘤生长暂时抑制1 ~ 10个月。在这些患者中，观察到CD 8 +HLA-DR+淋巴细胞和INF-γ+ CD 8+淋巴细胞的数量增加。结论：1.以DC为基础的免疫治疗在儿童难治性恶性肿瘤的治疗中可能是可行的、耐受性好的、有前景的方法. DC中的基因表达：为了阐明DCs的功能特性，研究成人外周血（APB）和脐带血（UCB）来源的DCs之间基因表达的差异。UCB-DCs中与免疫耐受建立相关的钙颗粒蛋白和细胞周期相关基因的表达明显高于APB-DCs，而APB-DCs中Th 1相关细胞因子基因的表达明显高于UCB-DCs。此外，炎性细胞因子基因的表达增加依赖于DC的成熟。结果提示UCB-和APB-DCs的免疫反应性存在功能差异。TNF-相关凋亡诱导配体（TRAIL）的抗白血病作用：TRAIL在mRNA和蛋白水平表达于静息状态的中性粒细胞，IFN-γ刺激后其表达增强。中性粒细胞在细胞表面表达TRAIL并将其分泌到培养基中。当Jurkat细胞（白血病细胞系）在IFN-γ存在下与中性粒细胞一起培养时，经历凋亡的Jurkat细胞的数量根据效应物：靶标比率而增加。通过向培养基中加入抗TRAIL抗体，这种细胞毒性被部分抑制。结果提示，中性粒细胞可能通过TRAIL发挥自身的抗肿瘤作用。

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.