Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, China; Department of Oncology, Liuzhou People's Hospital, Liuzhou, China.
Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, China.
Int Immunopharmacol. 2023 Oct;123:110775. doi: 10.1016/j.intimp.2023.110775. Epub 2023 Aug 8.
To determine the effect of X-ray irradiation combined with PD-1 immune checkpoint inhibitor administration on lung tissue injury in a mouse model and its potential mechanism.
In all, 20 C57BL/6J mice were randomly divided into four groups with five mice in each group: control group, PD-1 inhibitor group, irradiation group, and irradiation combined with PD-1 inhibitor group. Hematoxylin-eosin staining of the lung tissue was performed 30 days after the end of irradiation to evaluate the morphological and pathological changes in the tissue. Masson staining and analysis of hydroxyproline were used to evaluate the degree of pulmonary fibrosis. The levels of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor α(TNF-α) were evaluated by Enzyme-Linked immunosorbent assay (ELISA). CD3+, CD4+, and CD8+ T lymphocytes in the lung tissue were detected by immunohistochemistry. The expression levels of TGF-β1, Smad3, cGAS, and STING in the lung tissue were evaluated by Western blotting.
The lung injury scores and pulmonary fibrosis indices in the irradiation group were higher than those in the control group. Meanwhile, lung pneumonia score, pulmonary fibrosis index, percentage of CD4 cells and expression of TGF-β1, p-Smad3, and STING in the lung tissue of mice in irradiation combined with PD-1 inhibitor group were higher than those in the other three groups.
Lung injury and pulmonary fibrosis were induced by whole chest X-ray irradiation in mice, and PD-1 inhibitor could aggravate lung injury and pulmonary fibrosis in mice. Thus, radiotherapy combined with PD-1 inhibitors may affect the immune inflammatory microenvironment in the lung tissues of mice by activating TGF-β1/Samd3 and cGAS/STING signaling pathways, thus aggravating lung tissue damage induced by radiation.
探讨 X 射线照射联合 PD-1 免疫检查点抑制剂给药对小鼠肺部组织损伤的影响及其潜在机制。
将 20 只 C57BL/6J 小鼠随机分为 4 组，每组 5 只，分别为对照组、PD-1 抑制剂组、照射组和照射联合 PD-1 抑制剂组。照射结束后 30 天，对肺组织进行苏木精-伊红染色，评估组织的形态和病理变化。Masson 染色和羟脯氨酸分析用于评估肺纤维化程度。通过酶联免疫吸附试验（ELISA）评估转化生长因子-β1（TGF-β1）和肿瘤坏死因子α（TNF-α）的水平。免疫组织化学法检测肺组织中 CD3+、CD4+和 CD8+T 淋巴细胞。Western blot 法评估肺组织中 TGF-β1、Smad3、cGAS 和 STING 的表达水平。
照射组的肺损伤评分和肺纤维化指数高于对照组。同时，照射联合 PD-1 抑制剂组小鼠的肺炎评分、肺纤维化指数、CD4+细胞百分比以及肺组织中 TGF-β1、p-Smad3 和 STING 的表达均高于其他三组。
全胸 X 射线照射可诱导小鼠肺部损伤和肺纤维化，PD-1 抑制剂可加重小鼠肺部损伤和肺纤维化。因此，放疗联合 PD-1 抑制剂可能通过激活 TGF-β1/Smad3 和 cGAS/STING 信号通路，影响小鼠肺部组织的免疫炎症微环境，从而加重辐射引起的肺组织损伤。
