How does ionizing irradiation contribute to the induction of anti-tumor immunity?
How does ionizing irradiation contribute to the induction of anti-tumor immunity?
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DOI：
10.3389/fonc.2012.00075
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发表时间：
2012
影响因子：
4.7
通讯作者：
Gaipl US
中科院分区：
文献类型：
--
作者：
Rubner Y;Wunderlich R;Rühle PF;Kulzer L;Werthmöller N;Frey B;Weiss EM;Keilholz L;Fietkau R;Gaipl US
放射治疗(RT)结合电离辐射是肿瘤局部治疗的常用方法。它会导致癌细胞停止增殖，最终导致肿瘤细胞死亡。在过去的几年中，越来越明显的是，除了及时和局部限制的辐射诱导的免疫抑制外，针对肿瘤及其转移的特异性免疫激活是可以通过使肿瘤细胞可见的免疫攻击来实现的。免疫系统参与肿瘤控制，我们在这里概述了RT在低剂量应用时如何诱导抗炎，而在高剂量时如何在诱导抗肿瘤免疫中做出贡献。我们特别关注局部照射是如何引起非局域效应的。后者在一定程度上是由免疫系统对单个肿瘤细胞的系统性激活所介导的。树突状细胞是启动和调节适应性抗肿瘤免疫反应的关键细胞。他们必须摄取肿瘤抗原，并在适当的共同刺激下连续呈现肿瘤多肽。我们回顾了RT与其他免疫刺激物如AnnexinA5和热疗的结合如何促进树突状细胞介导的抗肿瘤免疫反应的诱导，并提出了标准肿瘤治疗与免疫治疗的合理组合方案。可以得出结论，RT可导致肿瘤细胞的靶向杀伤，并另外诱导非靶向的全身免疫效应。因此，多模式肿瘤治疗应倾向于在刺激免疫细胞的肿瘤微环境中诱导免疫原性肿瘤细胞死亡形式。
Radiotherapy (RT) with ionizing irradiation is commonly used to locally attack tumors. It induces a stop of cancer cell proliferation and finally leads to tumor cell death. During the last years it has become more and more evident that besides a timely and locally restricted radiation-induced immune suppression, a specific immune activation against the tumor and its metastases is achievable by rendering the tumor cells visible for immune attack. The immune system is involved in tumor control and we here outline how RT induces anti-inflammation when applied in low doses and contributes in higher doses to the induction of anti-tumor immunity. We especially focus on how local irradiation induces abscopal effects. The latter are partly mediated by a systemic activation of the immune system against the individual tumor cells. Dendritic cells are the key players in the initiation and regulation of adaptive anti-tumor immune responses. They have to take up tumor antigens and consecutively present tumor peptides in the presence of appropriate co-stimulation. We review how combinations of RT with further immune stimulators such as AnnexinA5 and hyperthermia foster the dendritic cell-mediated induction of anti-tumor immune responses and present reasonable combination schemes of standard tumor therapies with immune therapies. It can be concluded that RT leads to targeted killing of the tumor cells and additionally induces non-targeted systemic immune effects. Multimodal tumor treatments should therefore tend to induce immunogenic tumor cell death forms within a tumor microenvironment that stimulates immune cells.