Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Immunol. 2023 Mar 6;14:1112409. doi: 10.3389/fimmu.2023.1112409. eCollection 2023.
Immune checkpoint inhibitors (ICIs) alone or combined with other antitumor agents are largely used in lung cancer patients, which show both positive effects and side effects in particular subjects. Our study aims to identify biomarkers that can predict response to immunotherapy or risk of side effects, which may help us play a positive role and minimize the risk of adverse effects in clinical practice.
We retrospectively collected data from patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs at our center. Patients who received initial ICI therapy for >1 year without progression of disease were classified as long-term treatment (LT) group, while others were classified as the non-long-term treatment (NLT) group. Multivariate logistic analysis was performed to identify independent risk factors of progression-free survival (PFS) and immune-related adverse events (irAEs).
A total of 83 patients (55.7%) had irAEs. The median PFS for patients in grades 1-2 of irAEs vs. grades 3-4 vs non-irAEs groups was (undefined vs. 12 vs. 8 months; = 0.0025). The 1-year PFS rate for multisystem vs. single vs. non-irAE groups was 63%, 56%, and 31%, respectively. Signal transduction of inflammatory cytokines improves clinical prognosis through immunomodulatory function, but the benefit is also limited by the resulting organ damage, making it a complex immune balance. Serum biomarkers including EOS% of ≥ 1.15 (HR: 8.30 (95% CI, 2.06 to 33.42); = 0.003) and IFN-γ of ≥ 3.75 (HR: 5.10 (95% CI, 1.29 to 20.15), = 0.02) were found to be predictive for irAEs.
EOS% of ≥1.15% and IFN-γ of ≥3.75 ng/L were considered peripheral-blood markers for irAEs and associated with improved clinical outcomes for immunotherapy in patients with advanced NSCLC.
免疫检查点抑制剂（ICI）单独或与其他抗肿瘤药物联合用于肺癌患者，在特定患者中显示出积极作用和副作用。我们的研究旨在确定能够预测免疫治疗反应或副作用风险的生物标志物，这可能有助于我们在临床实践中发挥积极作用并最大程度地降低不良反应的风险。
我们回顾性收集了在我们中心接受 ICI 治疗的晚期非小细胞肺癌（NSCLC）患者的数据。将接受初始 ICI 治疗超过 1 年且无疾病进展的患者分为长期治疗（LT）组，而将其他患者分为非长期治疗（NLT）组。进行多变量逻辑分析以确定无进展生存期（PFS）和免疫相关不良事件（irAE）的独立危险因素。
共有 83 名患者（55.7%）出现 irAE。irAE 分级 1-2 级与 3-4 级与无 irAE 组的中位 PFS 分别为（未定义 vs. 12 vs. 8 个月；= 0.0025）。炎症细胞因子信号转导通过免疫调节功能改善临床预后，但益处也受到由此产生的器官损伤的限制，因此是一种复杂的免疫平衡。包括 EOS%≥1.15（HR：8.30（95%CI，2.06 至 33.42）；= 0.003）和 IFN-γ≥3.75（HR：5.10（95%CI，1.29 至 20.15），= 0.02）在内的血清生物标志物被发现可预测 irAE。
EOS%≥1.15%和 IFN-γ≥3.75ng/L 被认为是 irAE 的外周血标志物，与晚期 NSCLC 患者免疫治疗的临床结局改善相关。
