Characterization of pre- and on-treatment soluble immune mediators and the tumor microenvironment in NSCLC patients receiving PD-1/L1 inhibitor monotherapy.

IF 4.6 2区 医学 Q2 IMMUNOLOGY
Daiki Murata, Koichi Azuma, Kenta Murotani, Akihiko Kawahara, Yuuya Nishii, Takaaki Tokito, Tetsuro Sasada, Tomoaki Hoshino
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引用次数: 0

Abstract

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.

Conclusion: 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.

Abstract Image

接受 PD-1/L1 抑制剂单药治疗的 NSCLC 患者治疗前和治疗中可溶性免疫介质及肿瘤微环境的特征。
背景:尽管ICI单药治疗具有良好的疗效,但大多数非小细胞肺癌(NSCLC)患者并无反应。因此,确定哪些患者能从 ICI 治疗中获得最佳疗效仍是一项挑战:在接受 ICI 单药治疗的 183 例晚期或复发性 NSCLC 患者中,我们分析了 110 例可获得治疗前和治疗后血浆样本的患者。在开始接受 ICI 治疗时和 6 周后,我们测定了 73 种可溶性免疫介质。为了找出有用的生物标志物,我们分析了可溶性免疫介质在治疗前和治疗中的水平变化与患者生存期的关系。我们还分析了治疗前或治疗中生物标志物与irAE发展、PD-L1表达、CD8+ TIL密度以及中性粒细胞与淋巴细胞比值(NLR)的关系:单变量分析显示,治疗前生物标志物包括6种免疫介质,而治疗中生物标志物包括8种免疫介质。多变量分析显示,治疗前生物标志物包括4种免疫介质(CCL19、CCL21、CXCL5、CXCL10),而治疗中生物标志物包括5种免疫介质(CCL7、CCL19、CCL23、CCL25、IL-32)。IrAE 的发生与治疗期间 CCL23 的变化有关。PD-L1 的表达与治疗前 TNFSF13B 的水平和治疗中 CCL25 的变化有关。CD8+ TIL密度与治疗前的CXCL10水平相关,而NLR与治疗前的CCL13和CCL17水平相关:我们发现了几种可溶性免疫介质,它们是接受 ICI 单药治疗的 NSCLC 患者治疗前和治疗中生存的生物标志物。其中一些生物标志物与其他可能的预测因子相关,包括irAE的发展、PD-L1的表达、CD8+ TIL密度和NLR。需要进一步开展大规模研究,为接受 ICI 单药治疗的 NSCLC 患者建立生物标志物。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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