Purpose of Review

In the past decade, immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer treatment. With the continuing rise in the number of cancer patients eligible for ICIs, a corresponding rise in immune-related adverse events (irAEs) is occurring. IrAEs are inflammatory reactions against normal, healthy tissue that occur due to ICI-induced activation of the immune system. Although the exact immune pathogenesis driving irAE development remains unknown, we review the main proposed mechanisms, highlighting how they may inform irAE prediction and treatment.

Recent Findings

IrAEs are common and diverse, varying in incidence, timing, and severity. The possible mechanisms driving irAEs include (1) activation of cytotoxic T cells; (2) activation of B cells and increased autoantibody production; (3) direct molecular mimicry and off-target toxicity; (4) activation of intracellular signaling and pro-inflammatory cytokine production; and (5) environmental modifiers of immune system activation, including composition of the host gut microbiome. These mechanisms may help identify predictive biomarkers and targeted treatment strategies.

Summary

IrAEs are driven by multiple components of the immune system. More research is needed to understand their immunopathogenesis so that clinicians across all specialties may more effectively monitor and manage these increasingly common conditions.

中文翻译：

---

在接受免疫检查点抑制剂治疗的癌症患者中驱动免疫相关不良事件的机制

审查目的

在过去十年中，免疫检查点抑制剂 (ICI) 彻底改变了癌症治疗领域。随着符合 ICI 条件的癌症患者数量持续增加，免疫相关不良事件 (irAE) 也相应增加。IrAE 是由于 ICI 诱导的免疫系统激活而发生的针对正常健康组织的炎症反应。尽管驱动 irAE 发展的确切免疫发病机制仍然未知，但我们回顾了主要提出的机制，强调了它们如何为 irAE 预测和治疗提供信息。

最近的发现

IrAE 常见且多样，发生率、时间和严重程度各不相同。驱动 irAE 的可能机制包括 (1) 细胞毒性 T 细胞的激活；(2)激活B细胞，增加自身抗体的产生；(3) 直接分子拟态和脱靶毒性；(4) 激活细胞内信号和促炎细胞因子的产生；(5) 免疫系统激活的环境调节剂，包括宿主肠道微生物组的组成。这些机制可能有助于识别预测性生物标志物和靶向治疗策略。

概括

IrAE 由免疫系统的多个组成部分驱动。需要更多的研究来了解它们的免疫发病机制，以便所有专业的临床医生可以更有效地监测和管理这些日益常见的疾病。