实体瘤的辐射处理对中性粒细胞浸润和功能的影响：系统评价
The Effect of Radiation Treatment of Solid Tumors on Neutrophil Infiltration and Function: A Systematic Review
影响因子:6.50000
分区:医学1区 Top / 肿瘤学2区 核医学2区
发表日期:2024 Nov 01
作者:
Léon Raymakers, Thijs J Demmers, Gert J Meijer, I Quintus Molenaar, Hjalmar C van Santvoort, Martijn P W Intven, Jeanette H W Leusen, Patricia A Olofsen, Lois A Daamen
摘要
放射疗法（RT）启动局部和全身免疫反应，可诱导抗肿瘤免疫并提高免疫疗法的功效。嗜中性粒细胞是RT后浸润肿瘤的第一批免疫细胞之一，建议对初始抗肿瘤免疫反应至关重要。然而，肿瘤中的中性粒细胞与较差的结局有关，RT诱导的中性粒细胞浸润也可能改变肿瘤微环境（TME）的组成，而有利于肿瘤进展。为了提高癌症患者的RT功效，了解RT和中性粒细胞之间的相互作用很重要。在这里，我们使用患者研究和体内模型中的临床前鼠，回顾了有关RT如何影响实体瘤TME中嗜中性粒细胞的浸润和功能的文献。通常，发现中性粒细胞水平在RT后的第一天增加并达到最大水平，并且可以保持至3周的升高。大多数研究报告说，嗜中性粒细胞在RT后的TME中具有免疫抑制作用，是由中性粒细胞吲哚胺2,3-二氧酶1和精氨酸酶1的上调引起的，以及中性粒细胞外陷阱的形成。 RT还与中性粒细胞产生活性氧的增加有关，这既可以改善和抑制抗肿瘤的免疫力。此外，多种鼠模型在耗尽嗜中性粒细胞时显示出提高的RT功效，这表明嗜中性粒细胞在RT后具有原质表型。我们得出的结论是，在制定RT策略时，不应忽略中性粒细胞的作用，并且需要在特定的肿瘤类型中进行进一步研究。另外，可以利用中性粒细胞通过将RT与中性粒细胞靶向疗法相结合来提高RT功效。
Abstract
Radiation therapy (RT) initiates a local and systemic immune response which can induce antitumor 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 antitumor 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 patients with cancer 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 3 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 and arginase 1, as well as neutrophil extracellular trap formation. RT was also associated with increased reactive oxygen species production by neutrophils, which can both improve and inhibit antitumor immunity. In addition, multiple murine models showed improved RT efficacy when depleting neutrophils, suggesting that neutrophils have a protumor 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.