Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Nat Cancer. 2024 Apr;5(4):557-571. doi: 10.1038/s43018-024-00730-3. Epub 2024 Feb 15.
With immune checkpoint inhibitors (ICIs) becoming the mainstay of treatment for many cancers, managing their immune-related adverse events (irAEs) has become an important part of oncological care. This Review covers the clinical presentation of irAEs and crucial aspects of reversibility, fatality and long-term sequelae, with special attention to irAEs in specific patient populations, such as those with autoimmune diseases. In addition, the genetic basis of irAEs, along with cellular and humoral responses to ICI therapy, are discussed. Detrimental effects of empirically used high-dose steroids and second-line immunosuppression, including impaired ICI effectiveness, call for more tailored irAE-treatment strategies. We discuss open therapeutic challenges and propose potential avenues to accelerate personalized management strategies and optimize outcomes.
随着免疫检查点抑制剂（ICIs）成为许多癌症治疗的主要手段，管理其免疫相关不良反应（irAEs）已成为肿瘤治疗的重要组成部分。本文综述了 irAEs 的临床表现以及可逆性、死亡率和长期后遗症的关键方面，并特别关注特定患者人群（如自身免疫性疾病患者）中的 irAEs。此外，还讨论了 irAEs 的遗传基础，以及对 ICI 治疗的细胞和体液反应。经验性使用大剂量类固醇和二线免疫抑制的有害影响，包括对 ICI 疗效的损害，呼吁制定更具针对性的 irAE 治疗策略。我们讨论了开放性治疗挑战，并提出了潜在的途径，以加速个性化管理策略和优化结果。
