Heat-shock protein 70-dependent dendritic cell activation by 5-aminolevulinic acid-mediated photodynamic treatment of human glioblastoma spheroids in vitro.
Heat-shock protein 70-dependent dendritic cell activation by 5-aminolevulinic acid-mediated photodynamic treatment of human glioblastoma spheroids in vitro.
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热休克蛋白70依赖性的树突状细胞通过5-氨基乙烯酸介导的光动力治疗人胶质细胞瘤球体的体外光动力治疗。
DOI:
10.1038/bjc.2011.327
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发表时间:
2011-09-27
影响因子:
8.8
通讯作者:
Sorg, R. V.
中科院分区:
文献类型:
--
作者:
Etminan, N.;Peters, C.;Lakbir, D.;Buenemann, E.;Boerger, V.;Sabel, M. C.;Haenggi, D.;Steiger, H-J;Stummer, W.;Sorg, R. V.
T-cell responses contribute to the anti-tumoural effect of photodynamic therapy (PDT). For such responses to occur, dendritic cells (DCs) have to migrate to the tumour, take up tumour antigens and respond to danger signals with maturation, before they engage in T-cell activation. Here, we have studied the effect of 5-aminolevulinic acid (ALA)-mediated PDT on DCs in vitro in a human spheroid model of glioblastoma (GB). Spheroids of the GB cell lines U87 and U251 were treated with ALA/PDT, and effects on attraction, uptake of tumour antigens and maturation of DCs were studied. To block heat-shock protein-70 (HSP-70) on the spheroids, neutralising antibodies were used. 5-Aminolevulinic acid /PDT-treated GB spheroids attracted DCs that acquired tumour antigens from the spheroids effectively. Moreover, co-culture with ALA/PDT-treated spheroids induced DC maturation as indicated by the upregulation of CD83 and co-stimulatory molecules as well as increased T-cell stimulatory activity of the DCs. Heat-shock protein-70 was upregulated on the spheroids after ALA/PDT treatment. Uptake of tumour antigens and DC maturation induced by the ALA/PDT-treated spheroids were inhibited when HSP-70 was blocked. ALA/PDT treatment of glioma spheroids promotes the three initial steps of the afferent phase of adaptive immunity, which is at least partially mediated by HSP-70.
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