一种反映非小细胞肺癌伴恶性胸腔积液免疫检查点抑制剂治疗反应的新生物测定方法。

IF 4 2区 医学 Q2 ONCOLOGY Translational lung cancer research Pub Date : 2024-12-31 Epub Date: 2024-12-19 DOI:10.21037/tlcr-24-559
Ayako Takigami, Naoko Mato, Koichi Hagiwara, Makoto Maemondo
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引用次数: 0

摘要

背景:免疫检查点抑制剂(ICI)治疗延长了一部分晚期非小细胞肺癌(NSCLC)患者的生存期。肿瘤中程序性细胞死亡配体1 (PD-L1)的组织学定量是预测ICI治疗效果的一种广泛采用的标志物。然而,由于组织取样困难,其在恶性胸腔积液(MPE)患者中的应用有时具有挑战性。本研究的目的是确定MPE患者ICI治疗的新预测因素。方法:共纳入22例MPE患者。最初,我们调查了与总生存(OS)相关的胸腔积液的几个参数。接下来,我们试图在体外反映对ICI治疗的反应,设计了一个简单的共培养生物试验,其中肿瘤细胞和免疫细胞与纳武单抗共培养。通过流式细胞术确认nivolumab与T细胞的结合,并通过酶联免疫吸附试验评估释放的干扰素γ (IFN-γ)。结果:参数分析显示,所有患者白蛋白水平和淋巴细胞百分比与OS有显著相关。仅驱动基因突变阳性患者的血管内皮生长因子(VEGF)和高迁移率组盒1 (HMGB1)与OS呈负相关。体外生物测定表明,与对照抗体相比,结合尼伏单抗的T细胞主要产生IFN-γ。在22名患者中,12名患者在接受纳武单抗治疗后显示IFN-γ释放增加。尽管IFN-γ水平与OS之间缺乏显著相关性,但与没有IFN-γ释放的患者相比,有IFN-γ释放的患者的ICI治疗持续时间更长。结论:体外nivolumab治疗后IFN-γ释放的免疫测定可以在ICI治疗前识别应答者。
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A novel bioassay reflecting response to immune checkpoint inhibitor therapy in non-small cell lung cancer with malignant pleural effusion.

Background: Immune checkpoint inhibitor (ICI) therapy has prolonged the survival of a proportion of patients with advanced non-small cell lung cancer (NSCLC). Histological quantification of programmed cell death-ligand 1 (PD-L1) in tumors is a widely adopted marker for predicting the efficacy of ICI treatment. However, its use in patients with malignant pleural effusion (MPE) is occasionally challenging because of the difficulty of tissue sampling. The aim of this study was to identify new predictive factors for ICI treatment in patients with MPE.

Methods: A total of 22 patients with MPE were included. Initially, we surveyed several parameters of pleural effusion in relation to overall survival (OS). Next, we attempted to reflect the response to ICI treatment in vitro, a simple co-culture bioassay was designed, in which tumor cells and immune cells were co-cultured with nivolumab. Binding of nivolumab to T cells was confirmed by flow cytometry, and the released interferon-gamma (IFN-γ) was evaluated by enzyme-linked immunosorbent assay.

Results: The parameter analysis demonstrated that the levels of albumin and the percentage of lymphocyte were significantly correlated with OS in all patients. Vascular endothelial growth factor (VEGF) and high mobility group box 1 (HMGB1) were negatively correlated with OS in only driver gene mutation-positive patients. In vitro bioassay showed that nivolumab-binding T cells predominantly produced IFN-γ compared with control antibody. Of the 22 patients, 12 showed an increase in IFN-γ release after treatment with nivolumab. Despite the lack of significant correlations between IFN-γ levels and OS, the duration of ICI treatment tended to be longer in patients with IFN-γ release versus those without IFN-γ release.

Conclusions: This immune assay of IFN-γ release after treatment with nivolumab in vitro may identify responders prior to ICI treatment.

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来源期刊
CiteScore
7.20
自引率
2.50%
发文量
137
期刊介绍: Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.
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