放射治疗（RT）启动局部和全身免疫反应，可以诱导抗肿瘤免疫并提高免疫治疗效果。中性粒细胞是放疗后最先浸润肿瘤的免疫细胞之一，被认为对于最初的抗肿瘤免疫反应至关重要。然而，肿瘤中的中性粒细胞与不良预后相关，放疗诱导的中性粒细胞浸润也可能改变肿瘤微环境 (TME) 的组成，有利于肿瘤进展。为了提高癌症患者的放疗疗效，了解放疗和中性粒细胞之间的相互作用非常重要。在这里，我们利用患者研究和临床前小鼠体内模型回顾了关于放疗如何影响实体瘤 TME 中中性粒细胞的浸润和功能的文献。一般来说，发现中性粒细胞水平在放疗后的最初几天内增加并达到最高水平，并且可以保持升高长达三周。大多数研究报告称，放疗后 TME 中中性粒细胞具有免疫抑制作用，这是由于中性粒细胞吲哚胺 2,3-双加氧酶 1 (IDO1) 和精氨酸酶 1 (ARG1) 表达上调以及中性粒细胞胞外陷阱 (NET) 形成所致。 RT 还与中性粒细胞产生的活性氧 (ROS) 增加有关，这既可以改善也可以抑制抗肿瘤免疫力。此外，多种小鼠模型在消耗中性粒细胞时显示出放疗疗效的改善，表明中性粒细胞在放疗后具有促肿瘤表型。我们的结论是，在制定放疗策略时不应忽视中性粒细胞的作用，并且需要对特定肿瘤类型进行进一步研究。此外，通过将放疗与中性粒细胞靶向疗法相结合，可以利用中性粒细胞来增强放疗疗效。版权所有 © 2024。由 Elsevier Inc. 出版。

Radiotherapy (RT) initiates a local and systemic immune response which can induce anti-tumor immunity and improve immunotherapy efficacy. Neutrophils are among the first immune cells that infiltrate tumors after RT and are suggested to be essential for the initial anti-tumor immune response. However, neutrophils in tumors are associated with poor outcomes and RT induced neutrophil infiltration could also change the composition of the tumor microenvironment (TME) in favor of tumor progression. To improve RT efficacy for cancer patients it is important to understand the interplay between RT and neutrophils. Here, we review the literature on how RT affects the infiltration and function of neutrophils in the TME of solid tumors, using both patients studies and preclinical murine in vivo models. In general, it was found that neutrophil levels increase and reach maximal levels in the first days after RT and can remain elevated up to three weeks. Most studies report an immunosuppressive role of neutrophils in the TME after RT, caused by upregulated expression of neutrophil indoleamine 2,3-dioxygenase 1 (IDO1) and arginase 1 (ARG1), as well as neutrophil extracellular trap (NET) formation. RT was also associated with increased reactive oxygen species (ROS) production by neutrophils, which can both improve and inhibit anti-tumor immunity. In addition, multiple murine models showed improved RT efficacy when depleting neutrophils, suggesting that neutrophils have a pro-tumor phenotype after RT. We conclude that the role of neutrophils should not be overlooked when developing RT strategies and requires further investigation in specific tumor types. In addition, neutrophils can possibly be exploited to enhance RT efficacy by combining RT with neutrophil-targeting therapies.Copyright © 2024. Published by Elsevier Inc.