Takigami Ayako, Mato Naoko, Hagiwara Koichi, Maemondo Makoto
Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University Hospital, Shimotsuke, Tochigi, Japan.
Transl Lung Cancer Res. 2024 Dec 31;13(12):3267-3277. doi: 10.21037/tlcr-24-559. Epub 2024 Dec 19.
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.
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 , 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.
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. 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.
This immune assay of IFN-γ release after treatment with nivolumab may identify responders prior to ICI treatment.
免疫检查点抑制剂（ICI）疗法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治疗疗效的广泛采用的标志物。然而，由于组织采样困难，其在恶性胸腔积液（MPE）患者中的应用偶尔具有挑战性。本研究的目的是确定MPE患者ICI治疗的新预测因素。
共纳入22例MPE患者。首先，我们调查了与总生存期（OS）相关的几种胸腔积液参数。接下来，我们试图反映对ICI治疗的反应，设计了一种简单的共培养生物测定法，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纳武单抗与T细胞的结合，并通过酶联免疫吸附测定法评估释放的干扰素-γ（IFN-γ）。
参数分析表明，白蛋白水平和淋巴细胞百分比在所有患者中均与OS显著相关。血管内皮生长因子（VEGF）和高迁移率族蛋白B1（HMGB1）仅在驱动基因突变阳性患者中与OS呈负相关。生物测定表明，与对照抗体相比，纳武单抗结合的T细胞主要产生IFN-γ。在22例患者中，12例在接受纳武单抗治疗后IFN-γ释放增加。尽管IFN-γ水平与OS之间缺乏显著相关性，但IFN-γ释放的患者ICI治疗持续时间往往比未释放IFN-γ的患者更长。
这种纳武单抗治疗后IFN-γ释放的免疫测定法可能在ICI治疗前识别出反应者。
