免疫治疗药物对癌症患者认知功能的潜在影响。

Potential Effect of Immunotherapy Agents on Cognitive Function in Cancer Patients.

机构信息

Clinical Research Department, Centre François Baclesse, Caen, France.

Normandie University, UNICAEN, INSERM, ANTICIPE, Caen, France.

出版信息

J Natl Cancer Inst. 2020 Feb 1;112(2):123-127. doi: 10.1093/jnci/djz168.

Abstract

A paradigm shift is occurring in cancer therapy, where instead of targeting tumor cells, immunotherapy agents (IA) target the immune system to overcome cancer tolerance and to stimulate an antitumor immune response. IA using immune checkpoint inhibitors (CPI) or chimeric antigen receptor T-cells have emerged as the most encouraging approaches to treat cancer patients. CPI are reported to induce moderate-to-severe neurologic immune-related adverse events in less than 1% of patients, whereas chimeric antigen receptor T-cell therapy is associated with frequent neurological toxicities that can be severe or even fatal. Cognitive difficulties have been described following chemotherapy and targeted therapy, but not specifically explored in patients receiving IA. The aim of this review is to establish a picture of the first published studies suggesting some biological and physiopathological effects of IA on cognitive functions among cancer patients. The first results originate from a preclinical study evaluating the role of CPI associated with peripheral radiation on cognitive dysfunction and the recent discovery of the central nervous lymphatic system allowing leukocytes to penetrate the central nervous system. Evaluating possible side effects of IA on cognitive function will be an important challenge for future clinical trials and for better understanding the underlying mechanisms through preclinical animal models.

摘要

癌症治疗正在发生范式转变,免疫疗法药物(IA)不再针对肿瘤细胞,而是针对免疫系统,以克服癌症耐受并刺激抗肿瘤免疫反应。使用免疫检查点抑制剂(CPI)或嵌合抗原受体 T 细胞的 IA 已成为治疗癌症患者最有希望的方法。据报道,CPI 在不到 1%的患者中引起中度至重度神经免疫相关不良事件,而嵌合抗原受体 T 细胞疗法与频繁的神经毒性相关,这些毒性可能严重甚至致命。化疗和靶向治疗后已经描述了认知困难,但在接受 IA 治疗的患者中并未专门探讨。本综述的目的是建立第一张发表的研究图片,这些研究表明 IA 对癌症患者认知功能的一些生物学和生理病理学影响。最初的结果源于一项评估 CPI 联合外周辐射对认知功能障碍的作用的临床前研究,以及最近发现中枢淋巴系统允许白细胞穿透中枢神经系统。评估 IA 对认知功能的可能副作用将是未来临床试验的重要挑战,也是通过临床前动物模型更好地理解潜在机制的重要挑战。

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