Abstract:
The rise of cancer immunotherapy has been a milestone in clinical oncology. Above all, immune checkpoint inhibitor treatment (ICI) with monoclonal antibodies targeting programmed cell death protein 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) has improved survival rates for an increasing number of malignancies. However, despite the clinical benefits, ICI-related autoimmunity has become a significant cause of non-relapse-related morbidity and mortality. Neurological immune-related adverse events (irAE-n) are particularly severe toxicities with a high risk for chronic illness, long-term steroid dependency, and early ICI treatment termination. While the clinical characteristics of irAE-n are well described, little is known about underlying immune mechanisms and potential biomarkers. Recently, high frequencies of neuronal autoantibodies in patients with irAE-n have been reported, however, their clinical relevance is unclear. Here, we present a dataset on neuronal autoantibody profiles in ICI-treated cancer patients with and without irAE-n, which was generated to investigate the potential role of neuronal autoantibodies in ICI-induced autoimmunity. Between September 2017 and January 2022 serum samples of 29 cancer patients with irAE-n post-ICI treatment) and 44 cancer control patients without high-grade immune-related adverse events (irAEs, n = 44 pre- and post-ICI treatment) were collected and tested for a large panel of brain-reactive and neuromuscular autoantibodies using indirect immunofluorescence and immunoblot assays. Prevalence of autoantibodies was compared between the groups and correlated with clinical characteristics such as outcome and irAE-n manifestation. These data represent the first systematic comparison of neuronal autoantibody profiles between ICI-treated cancer patients with and without irAE-n, providing valuable information for both researchers and clinicians. In the future, this dataset may be valuable for meta-analyses on the prevalence of neuronal autoantibodies in cancer patients.
摘要:
癌症免疫治疗的兴起已成为临床肿瘤学的一个里程碑。最重要的是,免疫检查点抑制剂治疗(ICI)与单克隆抗体靶向程序性细胞死亡蛋白1(PD-1),程序性细胞死亡配体1(PD-L1),和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)提高了越来越多的恶性肿瘤的生存率。然而,尽管有临床益处,ICI相关的自身免疫已成为非复发相关的发病率和死亡率的重要原因。神经免疫相关不良事件(irAE-n)是特别严重的毒性,具有慢性疾病的高风险,长期依赖类固醇,并提前终止ICI治疗。虽然很好地描述了irAE-n的临床特征,对潜在的免疫机制和潜在的生物标志物知之甚少。最近,已经报道了irAE-n患者中神经元自身抗体的高频率,然而,其临床相关性尚不清楚.这里,我们提供了一个关于ICI治疗的有和没有irAE-n的癌症患者的神经元自身抗体谱的数据集,它的产生是为了研究神经元自身抗体在ICI诱导的自身免疫中的潜在作用。在2017年9月至2022年1月之间,29名接受irAE-n后ICI治疗的癌症患者的血清样本)和44名癌症对照患者,无高级别免疫相关不良事件(irAE,收集ICI治疗前后的n=44),并使用间接免疫荧光和免疫印迹测定法测试了一大批脑反应性和神经肌肉自身抗体。比较各组之间自身抗体的患病率,并与临床特征如结果和irAE-n表现相关。这些数据代表了ICI治疗的有和没有irAE-n的癌症患者之间神经元自身抗体谱的首次系统比较。为研究人员和临床医生提供有价值的信息。在未来,该数据集对于癌症患者神经元自身抗体患病率的荟萃分析可能是有价值的.