免疫检查点抑制剂的中枢神经系统副作用：临床前模型、遗传学与多模态治疗
CNS side effects of immune checkpoint inhibitors: preclinical models, genetics and multimodality therapy.
作者信息
McGinnis Gwendolyn J, Raber Jacob
机构信息
Department of Radiation Medicine, Oregon Health & Science University, OR, USA.
Department of Behavioral Neuroscience, Oregon Health & Science University, OR, USA.
出版信息
Immunotherapy. 2017 Sep;9(11):929-941. doi: 10.2217/imt-2017-0056.
Abstract
Following cancer treatment, patients often report behavioral and cognitive changes. Novel cancer immunotherapeutics have the potential to produce sustained cancer survivorship, meaning patients will live longer with the side effects of treatment. Given the role of inflammatory pathways in mediating behavioral and cognitive impairments seen in cancer, we aim in this review to discuss emerging evidence for the contribution of immune checkpoint blockade to exacerbate these CNS effects. We discuss ongoing studies regarding the ability of immune checkpoint inhibitors to reach the brain and how treatment responses to checkpoint inhibitors may be modulated by genetic factors. We further consider the use of preclinical tumor-models to study the role of tumor status in CNS effects of immune checkpoint inhibitors and multimodality therapy.
摘要
癌症治疗后，患者常常报告有行为和认知方面的变化。新型癌症免疫疗法有可能实现癌症的长期存活，这意味着患者会在伴有治疗副作用的情况下存活更长时间。鉴于炎症通路在介导癌症中出现的行为和认知障碍方面所起的作用，我们在本综述中的目的是讨论免疫检查点阻断作用加剧这些中枢神经系统效应的新证据。我们讨论了关于免疫检查点抑制剂进入大脑能力的正在进行的研究，以及基因因素如何可能调节对检查点抑制剂的治疗反应。我们还进一步考虑使用临床前肿瘤模型来研究肿瘤状态在免疫检查点抑制剂和多模态疗法的中枢神经系统效应中的作用。
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