The T-cell response is regulated by the balance between costimulatory and coinhibitory signals. Immune checkpoints are essential for efficient T-cell activation, but also for maintaining self-tolerance and protecting tissues from damage caused by the immune system, and for providing protective immunity. Modulating immune checkpoints can serve diametric goals, such that blocking a coinhibitory molecule can unleash anti-cancer immunity whereas stimulating the same molecule can reduce an over-reaction in autoimmune disease. The purpose of this review is to examine the regulation of T-cell costimulation and coinhibition, which is central to the processes underpinning autoimmunity, transplant rejection and immune evasion in cancer. We will focus on the immunomodulation agents that regulate these unwanted over- and under-reactions. The use of such agents has led to control of symptoms and slowing of progression in patients with rheumatoid arthritis, reduced rejection rates in transplant patients, and prolonged survival in patients with cancer. The management of immune checkpoint inhibitor treatment in certain challenging patient populations, including patients with pre-existing autoimmune conditions or transplant patients who develop cancer, as well as the management of immune-related adverse events in patients receiving antitumor therapy, is examined. Finally, the future of immune checkpoint inhibitors, including examples of emerging targets that are currently in development, as well as recent insights gained using new molecular techniques, is discussed. T-cell costimulation and coinhibition play vital roles in these diverse therapeutic areas. Targeting immune checkpoints continues to be a powerful avenue for the development of agents suitable for treating autoimmune diseases and cancers and for improving transplant outcomes. Enhanced collaboration between therapy area specialists to share learnings across disciplines will improve our understanding of the opposing effects of treatments for autoimmune disease/transplant rejection versus cancer on immune checkpoints, which has the potential to lead to improved patient outcomes.

T 细胞反应受共刺激和共抑制信号之间的平衡调节。免疫检查点对于有效激活 T 细胞至关重要，而且对于维持自身耐受性和保护组织免受免疫系统造成的损害，以及提供保护性免疫也是必不可少的。调节免疫检查点可以达到完全不同的目标，例如阻断共抑制分子可以释放抗癌免疫，而刺激相同分子可以减少自身免疫性疾病的过度反应。本综述的目的是检查 T 细胞共刺激和共抑制的调节，这对于支持癌症中自身免疫、移植排斥和免疫逃避的过程至关重要。我们将专注于调节这些不需要的过度反应和反应不足的免疫调节剂。使用此类药物可以控制类风湿性关节炎患者的症状并减缓其进展，降低移植患者的排斥率，并延长癌症患者的生存期。检查了某些具有挑战性的患者群体中免疫检查点抑制剂治疗的管理，包括预先存在自身免疫疾病的患者或发生癌症的移植患者，以及接受抗肿瘤治疗的患者的免疫相关不良事件的管理。最后，讨论了免疫检查点抑制剂的未来，包括目前正在开发的新兴靶点的例子，以及使用新分子技术获得的最新见解。T 细胞共刺激和共抑制在这些不同的治疗领域中发挥着至关重要的作用。靶向免疫检查点仍然是开发适用于治疗自身免疫性疾病和癌症以及改善移植结果的药物的有力途径。加强治疗领域专家之间的合作以分享跨学科的知识，将增进我们对自身免疫性疾病/移植排斥治疗与癌症治疗对免疫检查点的相反影响的理解，这有可能改善患者的治疗效果。