Low-dose radiation as a potential strategy for alleviating lung injury caused by radiotherapy combined with immunotherapy: A preclinical study

IF 4.9 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology Pub Date : 2025-02-22 DOI:10.1016/j.radonc.2025.110823

Yu Wang , Jing Zhang , Yao Liu , Han Jiang , Bibo Wu , Shasha Zhao , WeiWei Ouyang , Yinxiang Hu , Bing Lu , Shengfa Su

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引用次数: 0

Abstract

Background and Purpose

Radiotherapy combined with immunotherapy has been shown to improve thoracic tumor outcomes while increasing the risk of lung injury. Low-dose radiotherapy (LD-RT) has been proven efficient in managing inflammatory diseases. This study aims to investigate whether LD-RT might alleviate lung injury induced by radiotherapy combined with immunotherapy, and attempt to explore its underlying mechanisms thereby offering novel insights for clinical application.

Methods

To establish a mouse model of lung injury caused by radiotherapy combined with immunotherapy, C57 BL/6J mice received intraperitoneal injections of programmed death 1(PD-1) inhibitor weekly and a single dose of 15 Gy whole thoracic irradiation. Then they received a single dose of LD-RT at 1.0 Gy or 1.5 Gy on Day 14 or 28. The mice were euthanized on Day 42, and lung tissue samples were collected for HE, Masson’s trichrome, and immunohistochemical staining to evaluate lung tissue damage, fibrosis, and lymphocyte infiltration. The expression levels of cytokine were quantified by the enzyme-linked immunosorbent assay.

Results

Both low-dose of 1.0 Gy and 1.5 Gy attenuated lung injury caused by radiotherapy combined with PD-1 inhibitors, but 1.5 Gy was more effective. Compared with Day 14, LD-RT at 1.5 Gy on Day 28 was more effective in alleviating alveolar inflammation and reducing collagen deposition, and inhibiting lymphocyte infiltration and secretion of inflammatory cytokine in lung tissue.

Conclusion

Low-dose radiation alleviated lung injury caused by radiotherapy combined with PD-1 inhibitor, and the alleviating effect is closely related to the timing and dose of the radiotherapy administered.

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低剂量辐射作为减轻放疗联合免疫治疗引起的肺损伤的潜在策略：一项临床前研究

背景与目的：放疗联合免疫治疗已被证明可以改善胸部肿瘤的预后，同时增加肺损伤的风险。低剂量放疗（LD-RT）已被证明是治疗炎症性疾病的有效方法。本研究旨在探讨LD-RT是否可以减轻放疗联合免疫治疗引起的肺损伤，并试图探索其潜在机制，从而为临床应用提供新的见解。方法：建立放射联合免疫治疗肺损伤小鼠模型，C57 BL/6J小鼠腹腔注射程序性死亡1（PD-1）抑制剂，每周一次，单次剂量15 Gy全胸照射。然后在第14天或第28天接受单剂量1.0 Gy或1.5 Gy的LD-RT。第42天对小鼠实施安乐死，收集肺组织样本进行HE、马松三色染色和免疫组化染色，评估肺组织损伤、纤维化和淋巴细胞浸润情况。采用酶联免疫吸附法测定细胞因子的表达水平。结果：低剂量1.0 Gy和1.5 Gy均可减轻PD-1抑制剂联合放疗引起的肺损伤，但以1.5 Gy效果更好。与第14天相比，第28天1.5 Gy的LD-RT在减轻肺泡炎症、减少胶原沉积、抑制肺组织淋巴细胞浸润和炎性细胞因子分泌方面更有效。结论：低剂量放疗联合PD-1抑制剂可减轻放疗所致肺损伤，其减轻效果与放疗的时间和剂量密切相关。

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

Radiotherapy and Oncology 医学-核医学

CiteScore

10.30

自引率

10.50%

发文量

2445

审稿时长

45 days

期刊介绍： Radiotherapy and Oncology publishes papers describing original research as well as review articles. It covers areas of interest relating to radiation oncology. This includes: clinical radiotherapy, combined modality treatment, translational studies, epidemiological outcomes, imaging, dosimetry, and radiation therapy planning, experimental work in radiobiology, chemobiology, hyperthermia and tumour biology, as well as data science in radiation oncology and physics aspects relevant to oncology.Papers on more general aspects of interest to the radiation oncologist including chemotherapy, surgery and immunology are also published.