Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Int J Hyperthermia. 2022;39(1):796-805. doi: 10.1080/02656736.2022.2080873.
Improvements of heat-delivery systems have led to hyperthermia (HT) being increasingly recognized as an adjunct treatment modality also for brain tumors. But how HT affects the immune phenotype of glioblastoma cells is only scarcely known.
We therefore investigated the effect of HT, radiotherapy (RT), and the combination of both (RHT) on cell death modalities, immune checkpoint molecule (ICM) expression and release of the danger signal HSP70 of two human glioblastoma cell lines (U87 and U251) by using multicolor flow cytometry and ELISA. Hyperthermia was performed once or twice for 60-minute sessions reaching temperatures of 39 °C, 41 °C, and 44 °C, respectively. RT was administered with 5 x 2 Gy.
A hyperthermia chamber for cell culture t-flasks regulating the temperature a contact sensor was developed. While the glioblastoma cells were rather radioresistant, particularly in U251 cells, the combination of RT with HT significantly increased the percentage of apoptotic and necrotic cells for all temperatures examined and for both, single and double HT application. In line with that, an increased release of HSP 70 was seen only in U251 cells, mainly following treatment with HT at temperatures of 44 °C alone or in combination with RT. In contrast, immune suppressive (PD-L1, PD-L2, HVEM) and immune stimulatory (ICOS-L, CD137-L and Ox40-L) ICMs were significantly increased mostly on U87 cells, and particularly after RHT with 41 °C.
Individual assessment of the glioblastoma immune cell phenotype with regard to the planned treatment is mandatory to optimize multimodal radio-immunotherapy protocols including HT.
热传递系统的改进使得热疗（HT）作为脑肿瘤的辅助治疗方式越来越受到重视。然而，HT 如何影响胶质母细胞瘤细胞的免疫表型知之甚少。
因此，我们通过多色流式细胞术和 ELISA 研究了 HT、放疗（RT）和两者联合（RHT）对两种人胶质母细胞瘤细胞系（U87 和 U251）的细胞死亡方式、免疫检查点分子（ICM）表达和危险信号 HSP70 释放的影响。HT 治疗一次或两次，每次 60 分钟，温度分别达到 39°C、41°C 和 44°C。RT 给予 5×2Gy。
开发了一种用于细胞培养瓶的热室，可调节温度和接触传感器。虽然胶质母细胞瘤细胞对辐射具有较强的抗性，尤其是在 U251 细胞中，但 RT 与 HT 的联合应用显著增加了所有温度下和单次及双次 HT 应用后凋亡和坏死细胞的比例。与此一致的是，仅在 U251 细胞中观察到 HSP70 的释放增加，主要是在单独或与 RT 联合应用 44°C 的 HT 后。相比之下，免疫抑制性（PD-L1、PD-L2、HVEM）和免疫刺激性（ICOS-L、CD137-L 和 Ox40-L）ICM 主要在 U87 细胞上显著增加，尤其是在 41°C 的 RHT 后。
对于包括 HT 在内的多模态放免治疗方案，必须对胶质母细胞瘤免疫细胞表型进行个体化评估，以优化治疗方案。
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