Institute of Clinical Immunology SB RAMS, 14 Yadrintsevskaya Str., 630099 Novosibirsk, Russia.
Cell Immunol. 2013 Jul-Aug;284(1-2):146-53. doi: 10.1016/j.cellimm.2013.07.013. Epub 2013 Aug 2.
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.
最近的研究表明，树突状细胞（DCs）除了在触发适应性抗肿瘤免疫方面具有重要作用外，还具有直接的细胞毒性抗肿瘤活性。在这里，我们研究了在 IFNα 和 GM-CSF（IFN-DCs）存在的情况下生成的脑胶质瘤患者单核细胞来源的 DC。这些 DC 的特征是对 TRAIL 耐药的 HEp-2 细胞的细胞毒性活性降低。这种 DC 细胞毒性功能的损伤主要在高级别脑胶质瘤患者中观察到，与不良预后相关。在体外用双链人 DNA 以及 rIL-2 预处理 DC 可部分恢复患者 DC 细胞毒性的功能障碍。与健康供体相比，一部分高级别脑胶质瘤患者的 IFN-DC 也不能溶解原发性自身或同种异体神经胶质瘤细胞。我们的研究结果表明，DC 损伤可能有助于脑胶质瘤的肿瘤发病机制，并证明在探索作为神经胶质瘤癌症疫苗的 DC 时，评估和纠正 DC 细胞毒性功能的必要性。
