Geng Yichao, Su Shengfa, Cao Li, Yang Ting, Ouyang Weiwei, Liu Lingfeng, Wu Bibo, Zhang Qiuning, Lu Bing, Wang Xiaohu
The First School of Clinical Medicine, Lanzhou University, Lanzhou, People's Republic of China.
Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People's Republic of China.
J Inflamm Res. 2022 Jan 26;15:545-556. doi: 10.2147/JIR.S350112. eCollection 2022.
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.
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-β1 (TGF-β1) and interleukin-6 (IL-6) in lung tissue were evaluated by cytokine multiplex analysis.
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-β1 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-β1 level.
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-β1 expression, thereby affecting the immune-inflammatory microenvironment in the lungs.
本研究旨在评估程序性死亡受体1（PD-1）抑制剂对辐射诱导的肺损伤（RILI）小鼠模型肺组织形态和免疫系统的影响，并评估放射治疗与PD-1抑制之间的相互作用。
将20只C57BL/6小鼠随机分为四组，每组5只。小鼠分别接受抗小鼠PD-1单克隆抗体、全胸照射、两者联合或两者均不接受处理。通过苏木精-伊红染色评估肺组织形态和病理变化；通过Masson染色和羟脯氨酸分析评估肺纤维化；免疫组化检测肺组织中CD3+、CD4+和CD8+T淋巴细胞；通过细胞因子多重分析评估肺组织中转化生长因子-β1（TGF-β1）和白细胞介素-6（IL-6）的浓度。
接受全胸照射的小鼠肺损伤评分和肺纤维化指标高于对照小鼠。接受PD-1抑制剂加照射的小鼠肺组织炎症浸润评分、肺泡变形评分、胶原体积分数和羟脯氨酸含量均显著高于其他三组。同样，接受放射治疗和PD-1抑制剂的小鼠肺组织中CD3+和CD8+T细胞百分比以及IL-6和TGF-β1浓度显著高于其他组。然而，PD-1抑制剂与照射仅在TGF-β1水平升高方面存在显著相互作用。
小鼠全胸X线照射可导致肺损伤和纤维化，PD-1抑制剂可使其加重。放射治疗联合PD-1抑制剂可能通过协同上调TGF-β1表达加重RILI，从而影响肺内免疫炎症微环境。
