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.
Sorg, R. V.
中科院分区:
医学1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.

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T细胞反应有助于光动力疗法(PDT)的抗肿瘤作用。为了发生这样的反应,树突状细胞(DC)在参与T细胞激活之前,必须迁移到肿瘤,摄取肿瘤抗原,并对危险信号做出成熟的反应。在此,我们研究了5-氨基乙酰丙酸(ALA)介导的光动力疗法对体外培养的人胶质母细胞瘤(GB)模型树突状细胞(DC)的影响。用ALA/PDT处理GB细胞系U87和U251的球体,研究其对肿瘤抗原的吸引、摄取和DC成熟的影响。为了阻断球体上的热休克蛋白-70(HSP-70),使用了中和抗体。5-氨基乙酰丙酸/光动力疗法处理的GB球体能有效地吸引从球体获得肿瘤抗原的DC。此外,与ALA/PDT处理的球体共培养可诱导DC成熟,CD83和共刺激分子表达上调,DC的T细胞刺激活性增强。经ALA/PDT处理后,球体表面热休克蛋白-70表达上调。当HSP-70被阻断时,ALA/PDT处理的球体对肿瘤抗原的摄取和诱导的DC成熟受到抑制。ALA/PDT治疗胶质瘤球体促进了适应性免疫传入阶段的三个初始步骤,这至少部分是由HSP-70介导的。
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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