Natural killer (NK) cells are innate lymphoid cells that play an essential role in the anti-tumor response through immunosurveillance, multiple mechanisms of cytotoxicity and the synthesis of cytokines modulating the immune tumor microenvironment (TME). After the dramatic advances in immunotherapy targeting T cells including the success of checkpoint inhibitors or autologous chimeric antigen receptor (CAR) expressing T cells in clinical practice, NK cells have gained growing interest for the development of new therapies. Although NK cells have shown promising responses in leukemia patients, the effects of NK-targeted therapies are currently limited in the treatment of solid tumors. Thus, radiotherapy could provide a valuable solution to improve treatments targeting NK cells. Indeed, ionizing radiations represent a powerful immuno-modulator that can either induce a pro-inflammatory and anti-tumor TME, or conversely lead to immunosuppression of effector immune cells in favor of tumor growth and therapeutic escape, depending on how it is delivered and tumor models. However, the effects of ionizing radiation on NK cells are only partially understood. Therefore, we review the effects of radiotherapy on the NK cell-mediated anti-tumor response, and propose potential strategies to reinvigorate NK cells by combining radiotherapy with NK cell-targeted therapies.

中文翻译：

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结合放射疗法和 NK 细胞疗法：时机已经到来。

自然杀伤 (NK) 细胞是先天性淋巴细胞，通过免疫监视、多种细胞毒性机制以及调节免疫肿瘤微环境 (TME) 的细胞因子合成，在抗肿瘤反应中发挥重要作用。在针对 T 细胞的免疫疗法取得巨大进展（包括检查点抑制剂或表达自体嵌合抗原受体 (CAR) 的 T 细胞在临床实践中取得成功）之后，NK 细胞对新疗法的开发越来越感兴趣。尽管 NK 细胞在白血病患者中显示出有希望的反应，但 NK 靶向疗法目前在实体瘤的治疗中效果有限。因此，放射治疗可以为改善针对 NK 细胞的治疗提供有价值的解决方案。的确，电离辐射是一种强大的免疫调节剂，可以诱导促炎和抗肿瘤 TME，或者相反地导致效应免疫细胞的免疫抑制，有利于肿瘤生长和治疗逃逸，具体取决于其传递方式和肿瘤模型。然而，电离辐射对 NK 细胞的影响目前尚不完全清楚。因此，我们回顾了放疗对 NK 细胞介导的抗肿瘤反应的影响，并提出了通过将放疗与 NK 细胞靶向治疗相结合来重振 NK 细胞的潜在策略。电离辐射对 NK 细胞的影响目前尚不完全清楚。因此，我们回顾了放疗对 NK 细胞介导的抗肿瘤反应的影响，并提出了通过将放疗与 NK 细胞靶向治疗相结合来重振 NK 细胞的潜在策略。电离辐射对 NK 细胞的影响目前尚不完全清楚。因此，我们回顾了放疗对 NK 细胞介导的抗肿瘤反应的影响，并提出了通过将放疗与 NK 细胞靶向治疗相结合来重振 NK 细胞的潜在策略。