FLASH Irradiation Modulates Immune Responses and Accelerates Lung Recovery: A Single-Cell Perspective.

IF 14.3 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Hao Lu, Menghua Li, Cheng Quan, Caihui Li, Dawei Li, Zhihui Li, Jing Xu, Lihui Zhang, Qixiang Liu, Guofu Dong, Changzhen Wang
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引用次数: 0

Abstract

Radiation therapy (RT) is essential for treating thoracic malignancies but often causes significant lung damage. FLASH-RT, an ultra-high dose rate irradiation technique, shows potential in reducing radiation-induced lung injury (RILI) while maintaining tumor control. However, the underlying immune mechanisms remain poorly understood. This study investigates the immune and cellular responses to FLASH-RT versus conventional dose rate (CONV) RT during the early phase of RILI. Using single-cell RNA sequencing (scRNA-seq), a dynamic landscape of the lung microenvironment is pictured during RILI within one-week post-irradiation. The analysis reveals that FLASH-RT induces a more immediate but transient cellular response, while CONV-RT causes sustained inflammation. FLASH irradiation significantly reduces neutrophil infiltration compared to CONV irradiation, particularly within the pro-inflammatory Ccrl2+ subset. FLASH irradiation also triggers stronger activation of CD4+ CD40L+ Th cells, which are critical for regulating immune responses and balancing inflammation. Moreover, FLASH irradiation attenuates pro-inflammatory activation and intercellular signaling of Mefv⁺ monocytes, thereby restraining excessive macrophage-driven inflammation. Additionally, FLASH irradiation enhances TGF-β signaling and epithelial-mesenchymal transition (EMT) in alveolar type 1 (AT1) cells, promoting tissue repair. These findings highlight FLASH-RT's superior immune modulation and reparative potential, providing valuable insights into its clinical application for minimizing radiation damage and enhancing lung recovery.

闪光照射调节免疫反应和加速肺恢复:单细胞视角。
放射治疗(RT)是治疗胸部恶性肿瘤必不可少的,但往往造成严重的肺损伤。FLASH-RT是一种超高剂量率的照射技术,显示出在维持肿瘤控制的同时减少辐射性肺损伤(RILI)的潜力。然而,潜在的免疫机制仍然知之甚少。本研究探讨了在RILI早期对FLASH-RT和常规剂量率(CONV) RT的免疫和细胞反应。使用单细胞RNA测序(scRNA-seq),在照射后一周内绘制RILI期间肺微环境的动态景观。分析表明,FLASH-RT诱导更直接但短暂的细胞反应,而convr - rt引起持续的炎症。与CONV照射相比,FLASH照射显著减少中性粒细胞浸润,特别是在促炎性Ccrl2+亚群中。FLASH照射还会触发CD4+ CD40L+ Th细胞的更强激活,这对于调节免疫反应和平衡炎症至关重要。此外,FLASH照射可以减弱Mefv +单核细胞的促炎激活和细胞间信号传导,从而抑制过度的巨噬细胞驱动的炎症。此外,FLASH照射可增强肺泡1型(AT1)细胞的TGF-β信号传导和上皮-间质转化(EMT),促进组织修复。这些发现突出了FLASH-RT优越的免疫调节和修复潜力,为其在减少辐射损伤和促进肺恢复方面的临床应用提供了有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced Science
Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
18.90
自引率
2.60%
发文量
1602
审稿时长
1.9 months
期刊介绍: Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
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