Carr Aisling S, Vonberg Frederick William, Koay Shiwen, Young Kate, Shaw Heather, Olsson-Brown Anna, Willis Mark
Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Pract Neurol. 2025 Mar 14;25(2):116-126. doi: 10.1136/pn-2024-004327.
Immune checkpoint inhibition unleashes the power of the immune system against tumour cells. Immune checkpoint inhibitors (ICIs) block the inhibitory effects of cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed death protein 1 (PD-1), programmed death ligand 1 (PD-L1) and lymphocyte activation gene 3 (LAG-3) molecules on T-cells, and so enhance physiological cytotoxic effects. ICIs can significantly improve survival from cancers, including those previously associated with poor treatment response, such as metastatic melanoma. However, on-target off-tumour effects of ICIs result in immune-related adverse events. These toxicities are common and require new multidisciplinary expertise to manage. ICI neurotoxicity is relatively rare but ominous due to its severity, heterogenous manifestations and potential for long-term disability. Neurotoxic syndromes are novel and often present precipitously. Here, we describe ICI mechanisms of action, their impact on cancer outcomes and their frequency of immune-related adverse events. We focus particularly on neurotoxicity. We discuss the current appreciation of neurotoxic syndromes, management strategies and outcomes based on clinical expertise and consensus, multi-specialty guidance. The use of immunotherapy is expanding exponentially across multiple cancer types and so too will our approach to these cases.
免疫检查点抑制可释放免疫系统对抗肿瘤细胞的能力。免疫检查点抑制剂（ICIs）可阻断细胞毒性T淋巴细胞相关蛋白4（CTLA-4）、程序性死亡蛋白1（PD-1）、程序性死亡配体1（PD-L1）和淋巴细胞激活基因3（LAG-3）分子对T细胞的抑制作用，从而增强生理细胞毒性作用。ICIs可显著提高癌症患者的生存率，包括那些以前治疗反应较差的癌症，如转移性黑色素瘤。然而，ICIs的肿瘤外靶向效应会导致免疫相关不良事件。这些毒性很常见，需要新的多学科专业知识来处理。ICI神经毒性相对罕见，但因其严重性、表现异质性和长期致残可能性而后果严重。神经毒性综合征是新出现的，且往往突然出现。在此，我们描述了ICIs的作用机制、它们对癌症治疗结果的影响以及免疫相关不良事件的发生频率。我们特别关注神经毒性。我们基于临床专业知识和共识、多专业指南，讨论了目前对神经毒性综合征的认识、管理策略及治疗结果。免疫疗法在多种癌症类型中的应用正在呈指数级增长，我们对这些病例的处理方法也将如此。
