Supplementary Material for: Intraoperative Flurbiprofen Treatment Alters Immune Checkpoint Expression in Patients Undergoing Elective Thoracoscopic Resection of Lung Cancer

<b><i>Objectives:</i></b> This study aimed to determine the effect of intraoperative administration of flurbiprofen on postoperative levels of programmed death 1 (PD-1) in patients undergoing thoracoscopic surgery. <b><i>Materials and Methods:</i></b> In this prospective double-blind trial, patients were randomized to receive intralipid (control group, <i>n</i> = 34, 0.1 mL/kg, i.v.) or flurbiprofen axetil (flurbiprofen group, <i>n</i> = 34, 50 mg, i.v.) before induction of anesthesia. PD-1 levels on T cell subsets, inflammation, and immune markers in peripheral blood were examined before the induction of anesthesia (T₀) and 24 h (T₁), 72 h (T₂), and 1 week (T₃) after surgery. A linear mixed model was used to determine whether the changes from baseline values (T₀) between groups were significantly different. <b><i>Results:</i></b> The increases in the percentage of PD-1⁽⁺⁾CD8⁽⁺⁾ T cells observed at T₁ and T₂ in the control group were higher than those in the flurbiprofen group (T₁: 12.91 ± 1.65 vs. 7.86 ± 5.71%, <i>p</i> = 0.031; T₂: 11.54 ± 1.54 vs. 8.75 ± 1.73%, <i>p</i> = 0.004), whereas no differences were observed in the changes in the percentage of PD-1⁽⁺⁾CD4⁽⁺⁾ T cells at T₁ and T₂ between the groups. Moreover, extensive changes in the percentage of lymphocyte subsets and inflammatory marker concentrations were observed at T₁ and T₂ after surgery and flurbiprofen attenuated most of these changes. <b><i>Conclusions:</i></b> Perioperative administration of flurbiprofen attenuated the postoperative increase in PD-1 levels on CD8⁽⁺⁾ T cells up to 72 h after surgery, but not after this duration. The clinical relevance of changes in PD-1 levels to long-term surgical outcome remains unknown.

<b><i>研究目的：</i></b> 本研究旨在探究术中给予氟比洛芬对接受胸腔镜手术患者术后程序性死亡受体1（programmed death 1, PD-1）水平的影响。<b><i>材料与方法：</i></b> 本前瞻性双盲试验中，患者于麻醉诱导前被随机分配接受脂肪乳剂（对照组，<i>n</i> = 34，0.1 mL/kg，静脉注射）或氟比洛芬酯（氟比洛芬组，<i>n</i> = 34，50 mg，静脉注射）。分别于麻醉诱导前（T₀）、术后24小时（T₁）、术后72小时（T₂）及术后1周（T₃）检测外周血T细胞亚群上的PD-1水平、炎症及免疫标志物水平。采用线性混合模型分析两组相较于基线值（T₀）的变化是否存在显著差异。<b><i>研究结果：</i></b> 对照组在T₁和T₂时间点的PD-1⁺CD8⁺T细胞占比增幅显著高于氟比洛芬组（T₁：12.91±1.65 vs. 7.86±5.71%，<i>p</i> = 0.031；T₂：11.54±1.54 vs. 8.75±1.73%，<i>p</i> = 0.004）；而两组在T₁和T₂时间点的PD-1⁺CD4⁺T细胞占比变化无显著差异。此外，术后T₁及T₂时间点可见淋巴细胞亚群占比与炎症标志物浓度出现显著变化，氟比洛芬可缓解多数此类变化。<b><i>研究结论：</i></b> 围术期给予氟比洛芬可抑制术后72小时内CD8⁺T细胞上PD-1水平的升高，但该作用无法持续至72小时之后。PD-1水平变化与手术远期预后的临床相关性仍有待明确。