在晚期非小细胞肺癌患者中,12种不同细胞因子的血浆水平与PD-1抑制剂联合化疗的治疗反应相关。
Plasma levels of 12 different cytokines correlate to PD-1 inhibitor combined chemotherapy responses in advanced non-small-cell lung cancer patient.
发表日期:2023 Sep 08
作者:
Yun Peng, Qiufeng Qi, Ming Zhu, Yaping Zhang, Yanqing Bao, Yongping Liu
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
靶向抗程序性死亡受体1(PD-1)单克隆抗体与化疗相结合,在非小细胞肺癌(NSCLC)中显示出改善预后的效果。然而,需要注意的是,并非所有患者从这种治疗中受益,因此需要更可靠的疗效评估指标和潜在的预后预测因子。细胞因子作为免疫系统中的重要分子,在临床设置中被认为是潜在的生物标记物,但其精确的临床应用仍不清楚。本研究旨在评估患者血液样本中细胞因子水平是否与非小细胞肺癌患者接受抗PD-1单克隆抗体联合化疗的肿瘤反应及患者生存相关。本研究使用多微球流式荧光法测定了35例晚期NSCLC患者和26名健康个体的12种血浆细胞因子水平。采用非参数性Wilcoxon配对秩和检验分析了细胞因子水平与临床反应之间的关系。通过放射学结果评估和电话随访记录了所有患者的无进展生存时间(PFS)。使用Kaplan-Meier和log-rank检验生成了生存曲线,并使用受试者工作特征(ROC)分析确定了细胞因子的阈值。IL-6、IL-1β、IFN-γ、IL-12p70和TNF-α的表达水平在对照组中显著低于NSCLC组(p = 0.001,p = 0.0028,p = 0.019,p = 0.0001,p = 0.0021)。基线和4个疗程后高IL-10水平预示着较差的预后;此外,患者在两个疗程后高TNF-α水平提示耐药性。在接受四个疗程的免疫化疗的患者中,高IL-6和IFN-γ水平与较差的PFS相关。我们的研究表明,细胞因子可以作为预测接受抗PD-1联合化疗治疗的非小细胞肺癌患者疗效的检测指标。血浆中IL-10、TNF-α、IL-6和IFN-γ水平升高可能预示着更差的临床预后。版权所有©2023作者。由Elsevier B.V.出版,版权所有。
Targeted anti-programmed death receptor 1 (PD-1) monoclonal antibodies, when combined with chemotherapy, have shown improved outcomes in non-small cell lung cancer (NSCLC). However, it is important to note that not all patients benefit from this treatment, and there is a pressing need for more reliable efficacy measures and potential predictors of outcome. Cytokines, which are important molecules in the immune system, have been considered as potential biomarkers in clinical settings, but their precise clinical use remains unclear. In this study, our objective was to assess whether the levels of cytokines in the patient's blood sample are associated with tumor response to anti-PD-1 monoclonal antibodies combined with chemotherapy as well as the survival of patients with advanced non-small cell lung cancer.A total of 12 plasma cytokines were measured in advanced NSCLC patients (n = 35) and healthy individuals (n = 26) using multi-microsphere flow immunofluorescence. The relationship between cytokine levels and clinical response was analyzed using nonparametric Wilcoxon matched-pair ranked tests. Progression-free survival (PFS) time was recorded for all patients through radiographic outcome assessment and telephone follow-up. Survival curves were generated using the Kaplan-Meier and log-rank tests, and the thresholds for cytokines were determined using receiver operating characteristic analysis (ROC).The expression levels of interleukin IL-6, IL-1 β, IFN-γ, IL-12p70, and TNF-α were significantly lower in the control group than those in the NSCLC group (p = 0.001, p = 0.0028, p = 0.019, p = 0.0001, p = 0.0021). High IL-10 levels at baseline and after 4 cycles of treatment conferred a worse prognosis; in addition, high TNF-α levels in patients after two cycles of immunochemotherapy suggested drug resistance. High levels of IL-6 and IFN-γ in patients undergoing four cycles of immunochemotherapy were associated with worse PFS.Our study suggests that cytokines can serve as detection indicators for predicting efficacy in non-small cell lung cancer patients undergoing anti-PD-1 combined with chemotherapy treatment. Elevated levels of IL-10, TNF-α, IL-6, and IFN-γ in the plasma may indicate a higher likelihood of experiencing a worse clinical outcome.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.