Souri Zahra, Pakdel Farzad
Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Department of Oculo-Facial Plastic Surgery, Farabi Eye Hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
J Ophthalmic Vis Res. 2024 Sep 16;19(3):368-380. doi: 10.18502/jovr.v19i3.15047. eCollection 2024 Jul-Sep.
Immune checkpoints (ICPs) are essential regulators of the immune system, ensuring a delicate balance between self-tolerance and autoimmune responses. ICP therapy is a rapidly growing cancer treatment strategy that inhibits the interaction between ICPs and their ligands. This biological interaction increases the ability of the immune system in combating cancer. However, in some cases, the use of these agents may lead to immune hyperactivity and, subsequently, autoimmune diseases. Graves' disease (GD), thyroid eye disease (TED), and orbital myopathy are complex autoimmune disorders characterized by the production of autoantibodies. The emergence of these treatment-related adverse events underscore the critical need for a deeper understanding of the immune-checkpoint axis in autoimmune diseases. In this review article, we provide a comprehensive survey of the biological mechanisms of ICPs that are most frequently targeted in cancer therapy, including CTLA-4, PD-1, PDL-1, and LAG3. Furthermore, we investigate the latest scientific findings on the adverse events associated with the inhibition of these ICPs. This paper will particularly focus on the potential risks these complications pose to ocular and orbital tissues, which are a concern in the context of cancer treatment.
免疫检查点（ICPs）是免疫系统的重要调节因子，确保自身耐受与自身免疫反应之间的微妙平衡。免疫检查点疗法是一种迅速发展的癌症治疗策略，可抑制免疫检查点与其配体之间的相互作用。这种生物学相互作用增强了免疫系统对抗癌症的能力。然而，在某些情况下，使用这些药物可能会导致免疫亢进，进而引发自身免疫性疾病。格雷夫斯病（GD）、甲状腺眼病（TED）和眼眶肌病是复杂的自身免疫性疾病，其特征是产生自身抗体。这些与治疗相关的不良事件的出现凸显了深入了解自身免疫性疾病中免疫检查点轴的迫切需求。在这篇综述文章中，我们全面概述了癌症治疗中最常靶向的免疫检查点的生物学机制，包括细胞毒性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（PDL-1）和淋巴细胞活化基因3（LAG3）。此外，我们还研究了与抑制这些免疫检查点相关的不良事件的最新科学发现。本文将特别关注这些并发症对眼部和眼眶组织构成的潜在风险，这在癌症治疗背景下是一个值得关注的问题。
