Immune Checkpoints and Graves' Disease, Thyroid Eye Disease, and Orbital Myopathy: A Comprehensive Review

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.