胸腔放疗后同时服用抗 PD-1 与连续服用抗 PD-1 的比较分析:对肺组织损伤的影响

IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Dose-Response Pub Date : 2025-02-20 eCollection Date: 2025-01-01 DOI:10.1177/15593258251322324
Peng Yan, Zewen Wang, Yufeng Wang, Yongliang Liu, Anna Tong, Meili Sun
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引用次数: 0

摘要

胸腔放疗与免疫检查点抑制剂(ICIs)的联合治疗已显示出协同治疗效果,尽管会出现重叠的肺部毒性。我们利用程序性细胞死亡蛋白-1(PD-1)抗体在胸部放疗后的不同时间点建立了小鼠模型。血红素和伊红(HE)染色以及 TUNEL 染色用于肺组织损伤的形态学评估。支气管肺泡灌洗液(BALF)中的炎症细胞和细胞因子采用流式细胞仪和细胞计数珠阵列免疫分析法(CBA)进行分析。此外,还进行了免疫组化(IHC)和免疫荧光(IF)染色,以观察肺组织中炎性细胞的浸润情况。与延迟给药相比,胸部放疗后立即给药 PD-1 抗体会导致更严重的肺组织损伤。同期治疗导致 BALF 中淋巴细胞和中性粒细胞增加,炎性细胞因子水平升高。IHC 和 IF 分析显示,同期治疗组的中性粒细胞、巨噬细胞和淋巴细胞更为突出。PD-1 抗体与胸腔放疗同时进行时,肺损伤更为严重,这可能是由于联合治疗导致炎症加重。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparative Analysis of Concurrent vs Sequential Administration of anti-PD-1 Following Thoracic Radiotherapy: Impact on Lung Tissue Damage.

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.

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来源期刊
Dose-Response
Dose-Response PHARMACOLOGY & PHARMACY-RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
CiteScore
4.90
自引率
4.00%
发文量
140
审稿时长
>12 weeks
期刊介绍: Dose-Response is an open access peer-reviewed online journal publishing original findings and commentaries on the occurrence of dose-response relationships across a broad range of disciplines. Particular interest focuses on experimental evidence providing mechanistic understanding of nonlinear dose-response relationships.
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