Feng Enshan, Gao Haili, Su Wei, Yu Chunjiang
Fuxing Hospital, Capital Medical University, Beijing 100038, China.
Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
Neural Regen Res. 2012 Jul 5;7(19):1498-506. doi: 10.3969/j.issn.1673-5374.2012.19.009.
Immunotherapy may be used for the treatment of glioblastoma multiforme; however, the induced immune response is inadequate when either T cells or dendritic cells are used alone. In this study, we established a novel vaccine procedure in rats, using dendritic cells pulsed with C6 tumor cell lysates in combination with adoptive transfer of T lymphocytes from syngenic donors. On day 21 after tumor inoculation, all the rats were sacrificed, the brains were harvested for calculation of glioma volume, cytolytic T lymphocyte responses were measured by cytotoxic assay, and the frequency of regulatory T lymphocytes (CD4(+)CD25(+)FOXP3(+)) in the peripheral blood was investigated by flow cytometric analysis. The survival rate of rats bearing C6 glioma was observed. Results showed that the co-immunization strategy had significant anti-tumor potential against the pre-established C6 glioma, and induced a strong cytolytic T lymphocyte response in rats. The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period. Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.
免疫疗法可用于治疗多形性胶质母细胞瘤；然而，单独使用T细胞或树突状细胞时，诱导的免疫反应并不充分。在本研究中，我们在大鼠中建立了一种新型疫苗程序，使用用C6肿瘤细胞裂解物脉冲处理的树突状细胞，并联合同种基因供体的T淋巴细胞过继转移。在肿瘤接种后第21天，处死所有大鼠，取出大脑用于计算胶质瘤体积，通过细胞毒性试验测量细胞溶解性T淋巴细胞反应，并通过流式细胞术分析研究外周血中调节性T淋巴细胞（CD4(+)CD25(+)FOXP3(+)）的频率。观察携带C6胶质瘤的大鼠的存活率。结果表明，联合免疫策略对预先建立的C6胶质瘤具有显著的抗肿瘤潜力，并在大鼠中诱导了强烈的细胞溶解性T淋巴细胞反应。联合治疗后，外周血CD4(+)CD25(+)FOXP3(+)调节性T淋巴细胞的频率显著降低，且大鼠存活时间更长。实验结果表明，T细胞过继转移后进行胶质瘤细胞裂解物脉冲处理的树突状细胞疫苗联合免疫疗法可有效抑制大鼠胶质瘤的生长，增强抗肿瘤免疫力，并产生持续的免疫反应，同时避免CD4(+)CD25(+)FOXP3(+)调节性T淋巴细胞的积累。
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