Background:Previous preclinical data have shown that the dynamic cross-talk between abnormal tumor vasculature and immune cell factors in the tumor microenvironment may exert a critical role in the progression and treatment resistance of non-small cell lung cancer (NSCLC). In the clinical setting, a variety of blood-based angiogenesis- and immune-related factors are being increasingly investigated as potential biomarkers of prognosis or treatment response in immunotherapy-treated NSCLC. We herein aimed to evaluate the clinical relevance of the peripheral blood levels of vascular endothelial growth factor-A and -B (VEGF-A and VEGF-B, respectively), soluble programmed cell death-1 (sPD-1), and programmed cell death-ligand 1 (sPD-L1) in patients with advanced NSCLC treated with immune checkpoint inhibitors (ICIs).Methods:Consecutive patients with advanced-stage, non-oncogene-addicted NSCLC, eligible to receive ICIs at the Oncology Unit of Sotiria Athens General Hospital, were prospectively recruited. A group of sex- and age-matched healthy controls was also enrolled for the evaluation of the potential diagnostic significance of the examined biomarkers. Serum levels of all biomarkers were measured using ELISA, both before and after treatment, and were correlated with standard clinicopathological features of patients, treatment response, progression-free survival (PFS), and overall survival (OS).Results:A total of 55 patients and 16 healthy controls were included in the final analysis. The mean age of patients and controls was 66.5 years (SD = 8.0 years) and 65.4 years (SD = 9.1 years), respectively. The majority of patients (65.5%) received pembrolizumab in combination with chemotherapy, while the remaining patients received pembrolizumab monotherapy. ROC curve analysis showed that VEGFB and sPD-1 were the only markers with a significant diagnostic value. Higher pre-treatment values of sPD-L1 (HR = 1.68;p= 0.040) and sPD-1 (HR = 10.96;p= 0.037) as well as higher post-treatment values of VEGF-B (HR = 2.99;p= 0.049) were all significantly associated with a reduced OS in univariate Cox regression analysis. The adverse prognostic significance of higher pre-treatment values of sPD-L1 (HR = 2.10;p= 0.014) and higher post-treatment values of VEGFB (HR = 3.37;p= 0.032) was further confirmed in multivariate analysis.Conclusions:Our study results suggest that serum levels of sPD-L1 and VEGF-B may independently predict prognosis in ICI-treated advanced-stage NSCLC.
背景：既往临床前研究表明，肿瘤微环境中异常血管与免疫细胞因子之间的动态相互作用可能在非小细胞肺癌（NSCLC）的进展和治疗抵抗中发挥关键作用。在临床实践中，多种基于血液的血管生成和免疫相关因子正日益被研究作为免疫治疗NSCLC患者预后或治疗反应的潜在生物标志物。本研究旨在评估接受免疫检查点抑制剂（ICIs）治疗的晚期NSCLC患者外周血中血管内皮生长因子-A和-B（分别为VEGF-A和VEGF-B）、可溶性程序性细胞死亡蛋白-1（sPD-1）和程序性细胞死亡蛋白配体-1（sPD-L1）水平的临床相关性。 方法：前瞻性连续招募符合条件在雅典索提里亚综合医院肿瘤科接受ICIs治疗的晚期、非致癌基因成瘾性NSCLC患者。同时纳入一组性别和年龄匹配的健康对照者，以评估所检测生物标志物的潜在诊断价值。采用ELISA法测量所有生物标志物在治疗前和治疗后的血清水平，并将其与患者的标准临床病理特征、治疗反应、无进展生存期（PFS）和总生存期（OS）进行相关性分析。 结果：最终分析共纳入55例患者和16例健康对照者。患者和对照者的平均年龄分别为66.5岁（标准差=8.0岁）和65.4岁（标准差=9.1岁）。大多数患者（65.5%）接受了帕博利珠单抗联合化疗，其余患者接受了帕博利珠单抗单药治疗。ROC曲线分析显示，VEGF-B和sPD-1是唯一具有显著诊断价值的标志物。单变量Cox回归分析表明，较高的治疗前sPD-L1水平（风险比=1.68；p=0.040）和sPD-1水平（风险比=10.96；p=0.037），以及较高的治疗后VEGF-B水平（风险比=2.99；p=0.049）均与较短的OS显著相关。多变量分析进一步证实了较高的治疗前sPD-L1水平（风险比=2.10；p=0.014）和较高的治疗后VEGF-B水平（风险比=3.37；p=0.032）的不良预后意义。 结论：我们的研究结果表明，血清sPD-L1和VEGF-B水平可能独立预测接受ICI治疗的晚期NSCLC患者的预后。
肿瘤(癌症)患者之家