Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization.

Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization.
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发表时间:
2001-11
期刊:
影响因子:
11.2
通讯作者:
Y. Kotera;K. Shimizu;J. Mulé
Y. Kotera;K. Shimizu;J. Mulé
中科院分区:
医学1区
文献类型:
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作者:
Y. Kotera;K. Shimizu;J. Mulé

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对于免疫治疗应用中,坏死(裂解物)或凋亡肿瘤细胞是否作为多种肿瘤相关抗原(TAA)优于脉冲树突状细胞(DC)的来源存在相当大的争议。在这里,我们表明,通过 UVB 照射诱导细胞凋亡的标准程序明确会导致存活、凋亡和坏死肿瘤细胞的混合群体,因此需要额外的纯化。我们使用高度富集的 B16 黑色素瘤细胞凋亡与裂解物来检查这两种加载 DC 的 TAA 来源之间是否存在重要区别。我们的结果表明,尽管两种形式的TAA在热休克蛋白的表达以及脉冲DC产生白细胞介素12方面存在一些差异,但它们各自使DC表型成熟的能力,以及当DC呈现时在体内引发有效免疫启动和抗肿瘤治疗功效的能力是相同的。
There is considerable controversy as to whether necrotic (lysate) or apoptotic tumor cells serve as the superior source of multiple tumor-associated antigens (TAAs) to pulse dendritic cells (DCs) for immunotherapeutic applications. Here, we show that standard procedures to induce apoptosis by UVB irradiation unequivocally result in a mixed population of viable, apoptotic, and necrotic tumor cells, necessitating additional purification. We used highly enriched apoptotic versus lysate of B16 melanoma cells to examine whether or not there are important distinctions between these two sources of TAAs for loading of DCs. Our results demonstrate that although some differences exist between the two forms of TAAs in expression of heat shock proteins, as well as production of interleukin-12 by pulsed DCs, their respective capacities to mature DCs phenotypically, as well as to elicit both effective immune priming and antitumor therapeutic efficacy in vivo when presented by DCs, are equivalent.