在非小细胞肺癌患者中，循环特定细胞因子的基线水平是否与免疫检查点抑制（ICB）治疗的疗效有关仍未知。本研究收集了两个独立的、前瞻性的、多中心队列在ICB开始治疗之前的血清样本。共检测20种细胞因子，并通过接收者操作特征曲线分析确定截断值以预测非持久的益处。评估每个二分的细胞因子状态与生存结果之间的关联。在发现队列（阿特伯珠单抗队列；N = 81）中，根据IL-6（对数秩检验，P = 0.0014）、IL-15（P = 0.00011）、MCP-1（P = 0.013）、MIP-1β（P = 0.0035）和PDGF-AB/BB（P = 0.016）水平的差异，进展无瘤生存期（PFS）有显着性差异。其中，IL-6和IL-15水平在验证队列（尼伏单抗队列，N = 139）中也在PFS（对数秩检验，IL-6 P = 0.011，IL-15 P = 0.00065）和总生存期（OS；IL-6 P = 3.3E-6，IL-15 P = 0.0022）中具有显着的预后性。在合并队列中，IL-6高和IL-15高被确定为PFS和OS的独立不良预后因素。合并评估循环IL-6和IL-15水平的状态将患者生存结果分为三个不同的组，包括PFS和OS。总之，在基线时对循环IL-6和IL-15水平的联合评估提供了有价值的信息，以分层非小细胞肺癌患者接受ICB治疗的临床结果。需要进一步研究以解密这一发现的机制基础。©2023年。作者独家许可授权Springer-Verlag GmbH Germany，Springer Nature的一部分。

Whether circulating levels of specific cytokines at baseline link with treatment efficacy of immune checkpoint blockade (ICB) therapy in patients with non-small cell lung cancer remains unknown. In this study, serum samples were collected in two independent, prospective, multicenter cohorts before the initiation of ICB. Twenty cytokines were quantified, and cutoff values were determined by receiver operating characteristic analyses to predict non-durable benefit. The associations of each dichotomized cytokine status with survival outcomes were assessed. In the discovery cohort (atezolizumab cohort; N = 81), there were significant differences in progression-free survival (PFS) in accordance with the levels of IL-6 (log-rank test, P = 0.0014), IL-15 (P = 0.00011), MCP-1 (P = 0.013), MIP-1β (P = 0.0035), and PDGF-AB/BB (P = 0.016). Of these, levels of IL-6 and IL-15 were also significantly prognostic in the validation cohort (nivolumab cohort, N = 139) for PFS (log-rank test, P = 0.011 for IL-6 and P = 0.00065 for IL-15) and overall survival (OS; P = 3.3E-6 for IL-6 and P = 0.0022 for IL-15). In the merged cohort, IL-6high and IL-15high were identified as independent unfavorable prognostic factors for PFS and OS. The combined IL-6 and IL-15 status stratified patient survival outcomes into three distinct groups for both PFS and OS. In conclusion, combined assessment of circulating IL-6 and IL-15 levels at baseline provides valuable information to stratify the clinical outcome of patients with non-small cell lung cancer treated with ICB. Further studies are required to decipher the mechanistic basis of this finding.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.