Yan Peng, Wang Zewen, Wang Yufeng, Liu Yongliang, Tong Anna, Sun Meili
Department of Oncology, Jinan Central Hospital, Shandong First Medical University, Jinan, China.
Department of Radiation Oncology, 960 Hospital of the PLA Joint Logistics Support Force, Jinan, China.
Dose Response. 2025 Feb 20;23(1):15593258251322324. doi: 10.1177/15593258251322324. eCollection 2025 Jan-Mar.
The combination of thoracic radiotherapy and immune checkpoint inhibitors (ICIs) had demonstrated a synergistic therapeutic effect, albeit with the occurrence of overlapping pulmonary toxicities. We established a mouse model using programmed cell death protein-1 (PD-1) antibody at different time points after thoracic radiotherapy. Hematoxylin and eosin (HE) staining, as well as TUNEL staining, were utilized for the morphological assessment of lung tissue damage. Inflammatory cells and cytokines present in bronchoalveolar lavage fluid (BALF) were analyzed using flow cytometry and cytometric bead array immunoassay (CBA). Additionally, immunohistochemistry (IHC) and immunofluorescence (IF) staining were conducted to observe the infiltration of inflammatory cells in lung tissue. Immediate administration of PD-1 antibody after thoracic radiotherapy resulted in more severe lung tissue injury compared to delayed administration. Concurrent treatment led to an increase in lymphocytes and neutrophils in BALF, as well as higher levels of inflammatory cytokines. IHC and IF analysis revealed that neutrophils, macrophages, and lymphocytes were more prominent in the concurrent treatment group. A more severe lung injury occurred when PD-1 antibody was given simultaneously with thoracic radiotherapy, possibly due to increased inflammation caused by the combination treatment.
胸部放疗与免疫检查点抑制剂（ICIs）联合使用已显示出协同治疗效果，尽管会出现重叠的肺部毒性。我们在胸部放疗后的不同时间点使用程序性细胞死亡蛋白1（PD-1）抗体建立了小鼠模型。苏木精和伊红（HE）染色以及TUNEL染色用于对肺组织损伤进行形态学评估。使用流式细胞术和细胞计数珠阵列免疫分析（CBA）分析支气管肺泡灌洗液（BALF）中存在的炎性细胞和细胞因子。此外，进行免疫组织化学（IHC）和免疫荧光（IF）染色以观察肺组织中炎性细胞的浸润。与延迟给药相比，胸部放疗后立即给予PD-1抗体导致更严重的肺组织损伤。同时治疗导致BALF中淋巴细胞和中性粒细胞增加，以及炎性细胞因子水平升高。IHC和IF分析显示，同时治疗组中的中性粒细胞、巨噬细胞和淋巴细胞更为突出。当PD-1抗体与胸部放疗同时给予时，会发生更严重的肺损伤，这可能是由于联合治疗引起的炎症增加所致。
