CNS side effects of immune checkpoint inhibitors: preclinical models, genetics and multimodality therapy.

CNS side effects of immune checkpoint inhibitors: preclinical models, genetics and multimodality therapy.
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DOI:
10.2217/imt-2017-0056
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发表时间:
2017-09
期刊:
影响因子:
2.8
通讯作者:
Raber J
Raber J
中科院分区:
医学4区
文献类型:
--
作者:
McGinnis GJ;Raber J

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癌症治疗后,患者经常报告行为和认知变化。新型癌症免疫疗法有可能产生持续的癌症存活率,这意味着患者将在治疗副作用下活得更长。鉴于炎症途径在介导癌症中观察到的行为和认知障碍中的作用,我们在这篇综述中的目的是讨论免疫检查点阻断加剧这些CNS影响的新证据。我们讨论了正在进行的关于免疫检查点抑制剂到达大脑的能力以及遗传因素如何调节对检查点抑制剂的治疗反应的研究。我们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式治疗的CNS效应中的作用。
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.
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