Effect of PD-1 Inhibitor Combined with X-Ray Irradiation on the Inflammatory Microenvironment and Lung Tissue Injury in Mice

doi:10.2147/JIR.S350112

	Effect of PD-1 Inhibitor Combined with X-Ray Irradiation on the Inflammatory Microenvironment and Lung Tissue Injury in Mice
	Geng, Yichao 1,2,3; Su, Shengfa 2,3; Cao, Li 2; Yang, Ting 4; Ouyang, Weiwei 2,3; Liu, Lingfeng 2,3; Wu, Bibo 2,3; Zhang, Qiuning 5; Lu, Bing 2,3; Wang, Xiaohu 1,5
刊名	JOURNAL OF INFLAMMATION RESEARCH
	2022
卷号	15 页码:545-556
关键词	PD-1 inhibitors radiotherapy radiation fibrosis lung injury transforming growth factor-beta 1
DOI	10.2147/JIR.S350112
通讯作者	Lu, Bing(lbgymaaaa@163.com) ; Wang, Xiaohu(xhwang@impcas.ac.cn)
英文摘要	Purpose: This study was designed to evaluate the effects of PD-1 inhibitor on lung tissue morphology and the immune system in a mouse model of radiation-induced lung injury (RILI) and to assess interactions between radiation therapy and PD-1 inhibition. Methods: Twenty C57BL/6 mice were divided randomly into four groups of five mice each. Mice were treated with an anti-mouse PD-1 monoclonal antibody, whole thorax irradiation, both or neither. Lung tissue morphology and pathological changes were assessed by hematoxylin-eosin staining; lung fibrosis was assessed by Masson staining and analysis of hydroxyproline; CD3+, CD4+, and CD8+ T lymphocytes in lung tissues were detected immunohistochemically; and the concentrations of transforming growth factor-beta 1 (TGF-beta 1) and interleukin-6 (IL-6) in lung tissue were evaluated by cytokine multiplex analysis. Results: Lung injury scores and indicators of pulmonary fibrosis were higher in mice administration whole thorax irradiation than in control mice. Inflammatory infiltrate scores, alveoli deformation scores, collagen volume fractions and hydroxyproline contents in lung tissues were all significantly higher in mice administered PD-1 inhibitor plus irradiation than in the other three groups. Similarly, the percentages of CD3+ and CD8+T cells and the concentrations of IL-6 and TGF-beta 1 in lung tissue were significantly higher in mice treated with radiation and PD-1 inhibitor than in the other groups. However, PD-1 inhibitor and irradiation interacted significantly only in the elevation of TGF-beta 1 level. Conclusion: Whole thorax X-ray irradiation in mice can cause pulmonary injury and fibrosis, which could be exacerbated by PD-1 inhibitors. Radiotherapy combined with PD-1 inhibitors may aggravate RILI by synergistically upregulating TGF-beta 1 expression, thereby affecting the immune-inflammatory microenvironment in the lungs.
资助项目	Guizhou Provincial Natural Science Foundation, China[[2020] 1Y338] ; National Natural Science Foundation of China[81960548] ; Talent innovation and venture project of Lanzhou city[2021-RC-125]
WOS关键词	TGF-BETA ; MYOFIBROBLAST DIFFERENTIATION ; RADIATION-THERAPY ; MURINE STRAINS ; CANCER ; IMMUNOTHERAPY ; TOXICITY ; PROLIFERATION ; RADIOTHERAPY ; FIBROSIS
WOS研究方向	Immunology
语种	英语
出版者	DOVE MEDICAL PRESS LTD
WOS记录号	WOS:000748279400001
资助机构	Guizhou Provincial Natural Science Foundation, China ; National Natural Science Foundation of China ; Talent innovation and venture project of Lanzhou city
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/142117]
专题	中国科学院近代物理研究所
通讯作者	Lu, Bing; Wang, Xiaohu
作者单位	1.Lanzhou Univ, Sch Clin Med 1, Lanzhou, Peoples R China 2.Guizhou Med Univ, Dept Oncol, Affiliated Hosp, Guiyang, Peoples R China 3.Guizhou Med Univ, Dept Oncol, Affiliated Canc Hosp, Guiyang, Peoples R China 4.Guizhou Med Univ, Dept Pathophysiol, Guiyang, Peoples R China 5.Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China
推荐引用方式 GB/T 7714	Geng, Yichao,Su, Shengfa,Cao, Li,et al. Effect of PD-1 Inhibitor Combined with X-Ray Irradiation on the Inflammatory Microenvironment and Lung Tissue Injury in Mice[J]. JOURNAL OF INFLAMMATION RESEARCH,2022,15:545-556.
APA	Geng, Yichao.,Su, Shengfa.,Cao, Li.,Yang, Ting.,Ouyang, Weiwei.,...&Wang, Xiaohu.(2022).Effect of PD-1 Inhibitor Combined with X-Ray Irradiation on the Inflammatory Microenvironment and Lung Tissue Injury in Mice.JOURNAL OF INFLAMMATION RESEARCH,15,545-556.
MLA	Geng, Yichao,et al."Effect of PD-1 Inhibitor Combined with X-Ray Irradiation on the Inflammatory Microenvironment and Lung Tissue Injury in Mice".JOURNAL OF INFLAMMATION RESEARCH 15(2022):545-556.