Modern Radiotherapy Concepts and the Impact of Radiation on Immune Activation.
Modern Radiotherapy Concepts and the Impact of Radiation on Immune Activation.
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DOI：
10.3389/fonc.2016.00141
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发表时间：
2016
影响因子：
4.7
通讯作者：
Gaipl US
中科院分区：
文献类型：
--
作者：
Deloch L;Derer A;Hartmann J;Frey B;Fietkau R;Gaipl US
尽管在放射肿瘤学方面进行了广泛的研究，但大多数临床研究都集中在放射对局部肿瘤组织的影响上，并处理正常组织的副作用。到目前为止，剂量分割和时间的影响，特别是关于免疫激活的影响尚未得到令人满意的研究。因此，本文综述了现代放射治疗（RT）的概念，并评估了RT的免疫激活潜力。重点放在辐射诱导的肿瘤细胞死亡形式和连续的肿瘤细胞的免疫原性。所谓的非靶向、远位效应可以以特异性和全身性方式促进抗肿瘤反应，并具有靶向复发肿瘤细胞以及转移的能力。不同的RT概念对免疫激活的影响进行了概述，并将讨论临床前的证据和临床观察RT诱导的免疫。将考虑免疫细胞的放射敏感性知识以及RT后免疫增强的临床证据。虽然在临床前动物模型中，立体定向消融体放疗似乎比经典RT分割具有有益的结果，但体外模型系统表明经典分割RT在免疫激活方面具有优势。此外，最佳方法可以基于肿瘤部位和/或基因签名而不同。这些事实突出表明，迫切需要临床试验来确定与经典的分次RT相比，高剂量RT是否在诱导抗肿瘤免疫应答方面具有上级优势，特别是当RT与免疫疗法组合时，在选定的肿瘤实体中的结果如何。
Even though there is extensive research carried out in radiation oncology, most of the clinical studies focus on the effects of radiation on the local tumor tissue and deal with normal tissue side effects. The influence of dose fractionation and timing particularly with regard to immune activation is not satisfactorily investigated so far. This review, therefore, summarizes current knowledge on concepts of modern radiotherapy (RT) and evaluates the potential of RT for immune activation. Focus is set on radiation-induced forms of tumor cell death and consecutively the immunogenicity of the tumor cells. The so-called non-targeted, abscopal effects can contribute to anti-tumor responses in a specific and systemic manner and possess the ability to target relapsing tumor cells as well as metastases. The impact of distinct RT concepts on immune activation is outlined and pre-clinical evidence and clinical observations on RT-induced immunity will be discussed. Knowledge on the radiosensitivity of immune cells as well as clinical evidence for enhanced immunity after RT will be considered. While stereotactic ablative body radiotherapy seem to have a beneficial outcome over classical RT fractionation in pre-clinical animal models, in vitro model systems suggest an advantage for classical fractionated RT for immune activation. Furthermore, the optimal approach may differ based on the tumor site and/or genetic signature. These facts highlight that clinical trials are urgently needed to identify whether high-dose RT is superior to induce anti-tumor immune responses compared to classical fractionated RT and in particular how the outcome is when RT is combined with immunotherapy in selected tumor entities.