Department of Radiation Oncology, Friedrich-Alexander University of Erlangen-Nürnberg, Germany.
Radiother Oncol. 2011 Oct;101(1):109-15. doi: 10.1016/j.radonc.2011.05.056. Epub 2011 Jun 23.
Hyperthermia (HT) treatment of cancer patients was revived over the last years and has been proven to be beneficiary for many cancer entities when applied temperature controlled in multimodal treatments. We examined whether a combination of ionizing irradiation (X-ray) and HT (41.5°C; 1 h) can induce the release of heat shock protein (HSP) 70 by tumor cells and thereby lead to the activation of dendritic cells and macrophages.
Extracellular HSP70 was detected in supernatants (SN) of treated colorectal tumor cells by ELISA. Maturation of dendritic cells (DC) after contact with the SN was measured by flow-cytometry. Phagocytosis assays were conducted to get hints about the immune stimulating potential of the tumor cells after the respective treatments.
An increased surface expression of HSP70 was observed after X-ray or X-ray plus HT while the amount of extracellular HSP70 was only increased when HT was given additionally. A high up-regulation of the co-stimulation molecule CD80 and the chemokine receptor CCR7 on DC was measured after contact with SN of X-ray plus HT treated cells. This was dependent on extracellular HSP70. Combined treatments further led to significantly increased phagocytosis rates of macrophages and DC and increased pro-inflammatory cytokine (IL-8 and IL-12) secretion.
X-ray combined with HT induces HSP70 dependent activation of immune cells and might generate a tumor microenvironment beneficial for cure.
近年来，癌症患者的高温治疗（HT）得到了恢复，并已被证明在多种模式治疗中应用温度控制时对许多癌症实体有益。我们研究了电离辐射（X 射线）和 HT（41.5°C；1 小时）的联合应用是否可以诱导肿瘤细胞释放热休克蛋白（HSP）70，从而导致树突状细胞和巨噬细胞的激活。
通过 ELISA 检测处理的结直肠肿瘤细胞上清液（SN）中细胞外 HSP70 的含量。用流式细胞术测量与 SN 接触后树突状细胞（DC）的成熟情况。进行吞噬作用测定，以了解各自处理后肿瘤细胞的免疫刺激潜力。
X 射线或 X 射线加 HT 处理后观察到 HSP70 的表面表达增加，而仅在给予 HT 时才增加细胞外 HSP70 的量。与 X 射线加 HT 处理细胞的 SN 接触后，测量到共刺激分子 CD80 和趋化因子受体 CCR7 的高度上调。这依赖于细胞外 HSP70。联合治疗还导致巨噬细胞和 DC 的吞噬率显著增加，并增加了促炎细胞因子（IL-8 和 IL-12）的分泌。
X 射线联合 HT 诱导 HSP70 依赖性免疫细胞激活，并可能产生有利于治愈的肿瘤微环境。
