Modulating Both Tumor Cell Death and Innate Immunity Is Essential for Improving Radiation Therapy Effectiveness.
Modulating Both Tumor Cell Death and Innate Immunity Is Essential for Improving Radiation Therapy Effectiveness.
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DOI：
10.3389/fimmu.2017.00613
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发表时间：
2017
影响因子：
7.3
通讯作者：
Perfettini JL
中科院分区：
文献类型：
--
作者：
Wu Q;Allouch A;Martins I;Brenner C;Modjtahedi N;Deutsch E;Perfettini JL
放射治疗是癌症治疗的基石之一。在肿瘤细胞中，暴露于电离辐射（IR）会引起DNA损伤，从而引发各种形式的细胞死亡，如凋亡、坏死、自噬细胞死亡和有丝分裂灾难。IR还可以诱导细胞衰老，这可以作为一种额外的抗肿瘤屏障，以上下文依赖的方式。此外，越来越多的证据表明，IR与肿瘤浸润性免疫细胞相互作用，共同驱动治疗结果。由于放射治疗和免疫检查点阻断的结合，最近的临床前和临床成功强调了更好地理解放射治疗和免疫系统之间相互作用的必要性。在这篇综述中，我们将概述红外诱导的细胞死亡模式，总结辐照癌细胞的免疫原性，并讨论红外对先天免疫细胞功能的生物学影响，特别关注树突状细胞、巨噬细胞和NK细胞。最后，我们将讨论它们在癌症治疗中的潜在应用。
Radiation therapy is one of the cornerstones of cancer treatment. In tumor cells, exposure to ionizing radiation (IR) provokes DNA damages that trigger various forms of cell death such as apoptosis, necrosis, autophagic cell death, and mitotic catastrophe. IR can also induce cellular senescence that could serve as an additional antitumor barrier in a context-dependent manner. Moreover, accumulating evidence has demonstrated that IR interacts profoundly with tumor-infiltrating immune cells, which cooperatively drive treatment outcomes. Recent preclinical and clinical successes due to the combination of radiation therapy and immune checkpoint blockade have underscored the need for a better understanding of the interplay between radiation therapy and the immune system. In this review, we will present an overview of cell death modalities induced by IR, summarize the immunogenic properties of irradiated cancer cells, and discuss the biological consequences of IR on innate immune cell functions, with a particular attention on dendritic cells, macrophages, and NK cells. Finally, we will discuss their potential applications in cancer treatment.