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Inflammatory CNS disease caused by immune checkpoint inhibitors: status and perspectives
Nature Reviews Neurology ( IF 38.1 ) Pub Date : 2017-11-06 , DOI: 10.1038/nrneurol.2017.144
Lidia M. Yshii,Reinhard Hohlfeld,Roland S. Liblau

Cancer treatment strategies based on immune stimulation have recently entered the clinical arena, with unprecedented success. Immune checkpoint inhibitors (ICIs) work by indiscriminately promoting immune responses, which target tumour-associated antigens or tumour-specific mutations. However, the augmented immune response, most notably the T cell response, can cause either direct neurotoxicity or, more commonly, indirect neurotoxic effects through systemic or local inflammatory mechanisms or autoimmune mechanisms. Consequently, patients treated with ICIs are susceptible to CNS disease, including paraneoplastic neurological syndromes, encephalitis, multiple sclerosis and hypophysitis. In this Opinion article, we introduce the mechanisms of action of ICIs and review their adverse effects on the CNS. We highlight the importance of early detection of these neurotoxic effects, which should be distinguished from brain metastasis, and the need for early detection of neurotoxicity. It is crucial that physicians are well informed of these neurological adverse effects, given the anticipated increase in the use of immunotherapies to treat cancer.

中文翻译:

免疫检查点抑制剂引起的炎症性中枢神经系统疾病:现状和观点

基于免疫刺激的癌症治疗策略最近已进入临床领域,并取得了空前的成功。免疫检查点抑制剂(ICI)通过不加选择地促进针对肿瘤相关抗原或肿瘤特异性突变的免疫反应来发挥作用。但是,增强的免疫反应,最显着的是T细胞反应,可通过系统或局部炎症机制或自身免疫机制引起直接神经毒性,或更常见的是间接神经毒性作用。因此,接受ICI治疗的患者易患中枢神经系统疾病,包括副肿瘤神经综合症,脑炎,多发性硬化症和垂体炎。在这篇观点文章中,我们介绍了ICI的作用机制,并回顾了它们对中枢神经系统的不利影响。我们强调了这些神经毒性作用的早期检测的重要性,应将其与脑转移相区别,以及对神经毒性的早期检测的需求。鉴于使用免疫疗法治疗癌症的预期增加,使医生充分了解这些神经系统不良反应至关重要。
更新日期:2017-11-06
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