儿科肿瘤学中的免疫治疗相关神经毒性

Immunotherapy Associated Neurotoxicity in Pediatric Oncology.

作者信息

Shalabi Haneen, Nellan Anandani, Shah Nirali N, Gust Juliane

机构信息

National Cancer Institute, Pediatric Oncology Branch, National Institutes of Health, Bethesda, MD, United States.

Seattle Children's Research Institute, Seattle, WA, United States.

出版信息

Front Oncol. 2022 Feb 21;12:836452. doi: 10.3389/fonc.2022.836452. eCollection 2022.

Abstract

Novel immunotherapies are increasingly being employed in pediatric oncology, both in the upfront and relapsed/refractory settings. Through various mechanisms of action, engagement and activation of the immune system can cause both generalized and disease site-specific inflammation, leading to immune-related adverse events (irAEs). One of the most worrisome irAEs is that of neurotoxicity. This can present as a large spectrum of neurological toxicities, including confusion, aphasia, neuropathies, seizures, and/or death, with variable onset and severity. Earlier identification and treatment, generally with corticosteroids, remains the mainstay of neurotoxicity management to optimize patient outcomes. The pathophysiology of neurotoxicity varies across the different therapeutic strategies and remains to be elucidated in most cases. Furthermore, little is known about long-term neurologic sequelae. This review will focus on neurotoxicity seen with the most common immunotherapies used in pediatric oncology, including CAR T cell therapy, alternative forms of adoptive cell therapy, antibody therapies, immune checkpoint inhibitors, and tumor vaccines. Herein we will discuss the incidence, pathophysiology, symptomatology, diagnosis, and management strategies currently being utilized for immunotherapy-associated neurotoxicity with a focus on pediatric specific considerations.

摘要

新型免疫疗法越来越多地应用于儿童肿瘤学领域,无论是在初始治疗还是复发/难治性疾病的治疗中。通过各种作用机制,免疫系统的参与和激活可导致全身性和疾病部位特异性炎症,进而引发免疫相关不良事件(irAEs)。最令人担忧的irAEs之一是神经毒性。这可表现为一系列广泛的神经毒性,包括意识模糊、失语、神经病变、癫痫发作和/或死亡,其发作时间和严重程度各不相同。早期识别并通常使用皮质类固醇进行治疗,仍然是神经毒性管理的主要手段,以优化患者预后。神经毒性的病理生理学在不同的治疗策略中各不相同,在大多数情况下仍有待阐明。此外,关于长期神经后遗症知之甚少。本综述将聚焦于儿童肿瘤学中最常用的免疫疗法所导致的神经毒性,包括嵌合抗原受体(CAR)T细胞疗法、其他形式的过继性细胞疗法、抗体疗法、免疫检查点抑制剂和肿瘤疫苗。在此,我们将讨论目前用于免疫治疗相关神经毒性的发病率、病理生理学、症状学、诊断和管理策略,并重点关注儿童特有的注意事项。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e36/8899040/15a130d043f0/fonc-12-836452-g001.jpg

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