背景:尽管ICI单药治疗效果良好,大多数非小细胞肺癌(NSCLC)患者无反应.因此,确定能够从ICI治疗中最佳获益的患者仍然是一个挑战.
方法:在183名接受ICI单药治疗的晚期或复发NSCLC患者中,我们分析了110例治疗前和治疗后血浆样本可用的患者.在ICI开始和6周后测量73种可溶性免疫介质。为了识别有用的生物标志物,我们分析了治疗前水平和治疗中可溶性免疫介质的变化与患者生存率的关系.治疗前或治疗中的生物标志物与irAE发展的关联,PD-L1表达,CD8+TIL密度,还分析了中性粒细胞与淋巴细胞比率(NLR)。
结果:单变量分析表明,治疗前生物标志物包括6种免疫介质,而治疗中的生物标志物包括8种免疫介质.多因素分析显示,治疗前生物标志物包括4种免疫介质(CCL19、CCL21、CXCL5、CXCL10),而治疗中的生物标志物包括5种免疫介质(CCL7,CCL19,CCL23,CCL25,IL-32).IrAE的发展与CCL23的治疗改变有关。PD-L1表达与TNFSF13B的治疗前水平和CCL25的治疗中变化相关。CD8+TIL密度与治疗前CXCL10水平相关,而NLR与治疗前CCL13和CCL17水平相关。
结论:我们确定了几种可溶性免疫介质作为ICI单药治疗的NSCLC患者治疗前和治疗中的生存生物标志物。这些生物标志物中的一些与其他可能的预测因子相关,包括IRAE开发,PD-L1表达,CD8+TIL密度和NLR。需要进一步的大规模研究来建立接受ICI单药治疗的NSCLC患者的生物标志物。
BACKGROUND: Despite the favorable therapeutic efficacy observed with ICI monotherapy, the majority of non-small cell lung cancer (NSCLC) patients do not respond. Therefore, identifying patients who could optimally benefit from ICI treatment remains a challenge.
METHODS: Among 183 patients with advanced or recurrent NSCLC who received ICI monotherapy, we analyzed 110 patients whose pre- and post-treatment plasma samples were available. Seventy-three soluble immune mediators were measured at ICI initiation and 6 weeks later. To identify useful biomarkers, we analyzed the association of pre-treatment levels and on-treatment changes of soluble immune mediators with survival of patients. The associations of pre-treatment or on-treatment biomarkers with irAE development, PD-L1 expression, CD8+ TIL density, and neutrophil to lymphocyte ratio (NLR) were also analyzed.
RESULTS: Univariate analysis showed that pre-treatment biomarkers included 6 immune mediators, whereas on-treatment biomarkers included 8 immune mediators. Multivariate analysis showed that pre-treatment biomarkers included 4 immune mediators (CCL19, CCL21, CXCL5, CXCL10), whereas on-treatment biomarkers included 5 immune mediators (CCL7, CCL19, CCL23, CCL25, IL-32). IrAE development was associated with on-treatment change in CCL23. PD-L1 expression was associated with the pre-treatment levels of TNFSF13B and the on-treatment change in CCL25. CD8+ TIL density was associated with the pre-treatment CXCL10 level, whereas NLR was correlated with pre-treatment levels of CCL13 and CCL17.
CONCLUSIONS: We identified several soluble immune mediators as pre-treatment and on-treatment biomarkers of survival in patients with NSCLC treated with ICI monotherapy. Some of these biomarkers were associated with other possible predictors, including irAE development, PD-L1 expression, CD8+ TIL density and NLR. Further large-scale studies are needed to establish biomarkers for patients with NSCLC who received ICI monotherapy.