Immunotherapy has altered the therapeutic landscape for patients with non-small-cell lung cancer (NSCLC). The immune checkpoint inhibitor pembrolizumab targets the PD-1/PD-L1 signaling axis and produces durable clinical responses, but reliable biomarkers are lacking. Using 115 plasma samples from 42 pembrolizumab-treated patients with NSCLC, we were able to identify predictive biomarkers. In the plasma samples, we quantified the level of 92 proteins using the Olink proximity extension assay and circulating tumor DNA (ctDNA) using targeted next-generation sequencing. Patients with an above-median progression-free survival (PFS) had significantly higher expressions of Fas ligand (FASLG) and inducible T-cell co-stimulator ligand (ICOSLG) at baseline than patients with a PFS below the median. A Kaplan–Meier analysis demonstrated that high levels of FASLG and ICOSLG were predictive of longer PFS and overall survival (OS) (PFS: 10.83 vs. 4.49 months, OS: 27.13 vs. 18.0 months). Furthermore, we identified a subgroup with high expressions of FASLG and ICOSLG who also had no detectable ctDNA mutations after treatment initiation. This subgroup had significantly longer PFS and OS rates compared to the rest of the patients (PFS: 25.71 vs. 4.52 months, OS: 34.62 vs. 18.0 months). These findings suggest that the expressions of FASLG and ICOSLG at baseline and the absence of ctDNA mutations after the start of treatment have the potential to predict clinical outcomes.
免疫疗法已改变了非小细胞肺癌（NSCLC）患者的治疗格局。免疫检查点抑制剂帕博利珠单抗靶向PD-1/PD-L1信号轴并产生持久的临床应答，但尚缺乏可靠的生物标志物。通过分析42例接受帕博利珠单抗治疗的NSCLC患者的115份血浆样本，我们成功识别出预测性生物标志物。在血浆样本中，我们采用Olink邻位延伸检测技术对92种蛋白水平进行定量，并通过靶向二代测序检测循环肿瘤DNA（ctDNA）。结果显示，无进展生存期（PFS）高于中位值的患者，其基线期Fas配体（FASLG）和诱导性T细胞共刺激配体（ICOSLG）表达水平显著高于PFS低于中位值的患者。Kaplan-Meier分析表明，高水平的FASLG和ICOSLG能预测更长的PFS和总生存期（OS）（PFS：10.83个月 vs. 4.49个月；OS：27.13个月 vs. 18.0个月）。此外，我们识别出一个同时具有高FASLG/ICOSLG表达且治疗启动后未检出ctDNA突变的亚组，该亚组患者的PFS和OS率显著优于其他患者（PFS：25.71个月 vs. 4.52个月；OS：34.62个月 vs. 18.0个月）。这些发现提示，基线期FASLG与ICOSLG的表达水平及治疗启动后ctDNA突变的缺失，具有预测临床结局的潜力。
肿瘤(癌症)患者之家