Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Germany.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):1014-20. doi: 10.1016/j.bbrc.2009.12.008. Epub 2009 Dec 5.
Colorectal cancer is the second leading cause of death in developed countries. Tumor therapies should on the one hand aim to stop the proliferation of tumor cells and to kill them, and on the other hand stimulate a specific immune response against residual cancer cells. Dying cells are modulators of the immune system contributing to anti-inflammatory or pro-inflammatory responses, depending on the respective cell death form. The positive therapeutic effects of temperature-controlled hyperthermia (HT), when combined with ionizing irradiation (X-ray), were the origin to examine whether combinations of X-ray with HT can induce immune activating tumor cell death forms, also characterized by the release of the danger signal HMGB1. Human colorectal tumor cells with differing radiosensitivities were treated with combinations of HT (41.5 degrees C for 1h) and X-ray (5 or 10Gy). Necrotic cell death was prominent after X-ray and could be further increased by HT. Apoptosis remained quite low in HCT 15 and SW480 cells. X-ray and combinations with HT arrested the tumor cells in the radiosensitive G2 cell cycle phase. The amount of released HMGB1 protein was significantly enhanced after combinatorial treatments in comparison to single ones. We conclude that combining X-ray with HT may induce anti-tumor immunity as a result of the predominant induction of inflammatory necrotic tumor cells and the release of HMGB1.
结直肠癌是发达国家的第二大死亡原因。肿瘤治疗一方面应旨在阻止肿瘤细胞的增殖和杀死它们，另一方面刺激针对残留癌细胞的特异性免疫反应。死亡细胞是免疫系统的调节剂，根据各自的细胞死亡形式，促进抗炎或促炎反应。温度控制热疗（HT）与电离辐射（X 射线）联合的积极治疗效果是研究 X 射线与 HT 联合是否能诱导免疫激活的肿瘤细胞死亡形式的起源，其特征还在于危险信号 HMGB1 的释放。用 HT（41.5°C 持续 1 小时）和 X 射线（5 或 10Gy）联合处理具有不同放射敏感性的人结直肠肿瘤细胞。X 射线后坏死细胞死亡明显增加，HT 可进一步增加。HCT 15 和 SW480 细胞中的细胞凋亡仍然相当低。X 射线和 HT 联合治疗使肿瘤细胞在放射敏感的 G2 细胞周期阶段停滞。与单一治疗相比，联合治疗后释放的 HMGB1 蛋白明显增加。我们得出结论，X 射线与 HT 的联合治疗可能会由于炎症性坏死肿瘤细胞的主要诱导和 HMGB1 的释放而诱导抗肿瘤免疫。
