High hydrostatic pressure induces immunogenic cell death in human tumor cells
High hydrostatic pressure induces immunogenic cell death in human tumor cells
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DOI：
10.1002/ijc.28766
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发表时间：
2014-09-01
影响因子：
6.4
通讯作者：
Spisek, Radek
中科院分区：
文献类型：
--
作者：
Fucikova, Jitka;Moserova, Irena;Spisek, Radek
最近的研究已经确定了免疫原性细胞死亡（ICD）的分子事件特征，包括钙网蛋白（CRT）的表面暴露，热休克蛋白HSP 70和HSP 90，高迁移率族蛋白1（HMGB 1）的释放和ATP从垂死细胞的释放。我们研究了高静水压（HHP）诱导人肿瘤细胞ICD的潜力。HHP诱导细胞表面HSP 70、HSP 90和CRT的快速表达。HHP还能诱导HMGB 1和ATP的释放。树突状细胞（DC）与HHP处理的肿瘤细胞的相互作用导致DC吞噬作用的更快速率，CD 83、CD 86和HLA-DR的上调以及白细胞介素IL-6、IL-12 p70和TNF-α的释放。用HHP杀死的肿瘤细胞脉冲的DC诱导大量的肿瘤特异性T细胞。用HHP处理的肿瘤细胞脉冲的DC也诱导最低数量的调节性T细胞。此外，我们发现内质网应激介导的凋亡途径的关键特征，如活性氧的产生，翻译起始因子eIF 2 α的磷酸化和caspase-8的活化，被HHP处理激活。因此，HHP在人肿瘤细胞中充当ICD的可靠且有效的诱导剂。
Recent studies have identified molecular events characteristic of immunogenic cell death (ICD), including surface exposure of calreticulin (CRT), the heat shock proteins HSP70 and HSP90, the release of high-mobility group box protein 1 (HMGB1) and the release of ATP from dying cells. We investigated the potential of high hydrostatic pressure (HHP) to induce ICD in human tumor cells. HHP induced the rapid expression of HSP70, HSP90 and CRT on the cell surface. HHP also induced the release of HMGB1 and ATP. The interaction of dendritic cells (DCs) with HHP-treated tumor cells led to a more rapid rate of DC phagocytosis, upregulation of CD83, CD86 and HLA-DR and the release of interleukin IL-6, IL-12p70 and TNF-alpha. DCs pulsed with tumor cells killed by HHP induced high numbers of tumor-specific T cells. DCs pulsed with HHP-treated tumor cells also induced the lowest number of regulatory T cells. In addition, we found that the key features of the endoplasmic reticulum stress-mediated apoptotic pathway, such as reactive oxygen species production, phosphorylation of the translation initiation factor eIF2 alpha and activation of caspase-8, were activated by HHP treatment. Therefore, HHP acts as a reliable and potent inducer of ICD in human tumor cells.