Kramer Gero, Steiner Georg E, Gröbl Marion, Hrachowitz Kristian, Reithmayr Franz, Paucz Ljubomir, Newman Martin, Madersbacher Stephan, Gruber Diego, Susani Martin, Marberger Michael
Department of Urology, University of Vienna, Austria.
Prostate. 2004 Feb 1;58(2):109-20. doi: 10.1002/pros.10314.
To investigate the possibilities offered by high intensity focused ultrasound (HIFU) in the field of tumor vaccination, we analyzed how prostatic cancer (CaP) cells react towards heat treatment and whether increased access to CaP cells by the immune system would be the result.
Heat/stress response of CaP cells in situ and of CaP cell lines was analyzed by immunohistochemistry, Western blotting, and Atlas array. A heat-induced change in immune recognition was analyzed functionally using human T-helper (Th)1 and Th2-cytokine release with tumor infiltrating T-lymphocytes (TIL) as responder and autologous CaP cells either heated or untreated as stimulator cells.
Transcription of 68 out of 500 genes was upregulated by sublethal heat in LNCaP and PC3 cells. Significantly upregulated stress protein (SP) expression (HSP-72, -73, GRP-75, -78) was seen at the border zone of HIFU treatment. Remarkably, even untreated benign prostatic hyperplasia (BPH) specimens revealed relative overexpression of heat shock protein (HSP)-72, -73 and glucose regulated protein (GRP)-75, -78. Heated CaP cells increased Th1-cytokine (IL-2, IFN-gamma, TNF-alpha) release but decreased Th2-cytokine (IL-4, -5, -10) release of TIL.
HIFU treatment may alter the presentation of prostate tissue and tumor antigens and this presentation is most likely stimulatory. HSP-72/73 overexpression in untreated BPH may suggest a mechanism by which BPH can incite inflammation.
为了研究高强度聚焦超声（HIFU）在肿瘤疫苗领域的应用可能性，我们分析了前列腺癌细胞（CaP）对热处理的反应，以及免疫系统对CaP细胞的接触增加是否会产生相应结果。
通过免疫组织化学、蛋白质印迹法和Atlas芯片分析原位CaP细胞和CaP细胞系的热/应激反应。使用人辅助性T细胞（Th）1和Th2细胞因子释放，以肿瘤浸润性T淋巴细胞（TIL）作为反应细胞，加热或未处理的自体CaP细胞作为刺激细胞，从功能上分析热诱导的免疫识别变化。
在LNCaP和PC3细胞中，500个基因中有68个基因的转录在亚致死热作用下上调。在HIFU治疗的边界区域可见应激蛋白（SP）表达显著上调（HSP-72、-73、GRP-75、-78）。值得注意的是，即使未处理的良性前列腺增生（BPH）标本也显示热休克蛋白（HSP）-72、-73和葡萄糖调节蛋白（GRP）-75、-78的相对过表达。加热的CaP细胞增加了TIL的Th1细胞因子（IL-2、IFN-γ、TNF-α）释放，但减少了Th2细胞因子（IL-4、-5、-10）释放。
HIFU治疗可能会改变前列腺组织和肿瘤抗原的呈递，且这种呈递很可能具有刺激作用。未处理的BPH中HSP-72/73的过表达可能提示BPH引发炎症的一种机制。
