PD-1抑制剂诱发的药物免疫相关不良反应事件的研究

Detection of immune-related adverse events of PD-1 inhibitors

摘要:

近年来出现的肿瘤免疫治疗彻底改变传统的癌症治疗方法。免疫疗法是免疫抑制剂针对免疫检查点进行调节，免疫抑制剂包括细胞毒性T淋巴细胞抗原肿瘤4（CTLA-4）抑制剂、程序性死亡蛋白1（PD-1）抑制剂和程序性死亡蛋白配体1（PD-L1）抑制剂。PD-1/PD-L1抑制剂通过阻断PD-1/PD-L1途径以调节免疫耐受的重要抑制通路，在机体中参与维持对自身抗原的免疫耐受。然而，免疫系统平衡的转变也会对多个组织器官产生免疫相关不良事件（irAEs）。irAEs不同于传统的化疗药物或靶向治疗的副作用，且目前在其诊断和管理方面经验相对较少。因此，irAEs构成免疫疗法中真正的挑战，并且任何新的改变都可能是与治疗相关的。最常见的irAEs发生在皮肤、胃肠道，其次是肺、内分泌系统、肌肉骨骼、肾、神经、血液和心血管。IrAEs通常持续时间长、可控，但有时可能导致免疫治疗的中断，甚至可能发生致命不良事件。该文针对目前PD-1抑制剂所产生的irAEs做一综述。

Abstract:

The emergence of immunotherapy in recent years has revolutionized traditional cancer treatment. Immunotherapy is just an immunosuppressant that regulates immune checkpoints. Immunosuppressive agents include cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors, programmed cell death-1 (PD-1) inhibitors and programmed cell death ligand-1 (PD-L1) inhibitor. PD-1 / PD-L1 agents are involved in the maintenance of immune tolerance to autoantigens by blocking the PD-1 / PD-L1 pathway to regulate important inhibitory pathways of immune tolerance. However, a shift in the balance of the immune system can also develop immune-related adverse events (irAEs) in multiple tissues and organs. IrAEs differ from traditional chemotherapeutic drugs or the side effects of targeted therapies, and currently have relatively little experience in their diagnosis and management. Therefore, irAEs constitute a real challenge in immunotherapy, and any further changes may be related to treatment. The most common irAEs occurs in the skin, the gastrointestinal tract, attended by the lungs, endocrine system, musculoskeletal, kidney, nerve, blood, and cardiovascular. IrAEs are usually transient and controllable, but can sometimes lead to disruption of immunotherapy and may even cause fatal adverse events (FAE). This article is a review of current irAEs produced by PD-1 inhibitors.