除了免疫检查点 (ICP) 抑制剂在癌症治疗中取得的令人鼓舞的结果和广泛的临床适用性之外，基于 ICP 的免疫疗法在自身免疫性疾病，特别是多发性硬化症 (MS) 中也引起了相当大的关注，并且在开发有效的治疗策略方面具有巨大的潜力。鉴于 ICP 在维持刺激性和抑制性信号通路之间的平衡以促进对自身抗原的免疫耐受方面具有明确的免疫调节作用，在相当大比例的 MS 患者及其称为 MS 的动物模型中观察到 ICP 的表达失调模式。实验性自身免疫性脑脊髓炎（EAE），与髓磷脂和神经退行性变的自身反应有关。因此，开发免疫治疗策略来诱导抑制性 ICP，同时抑制刺激性 ICP，包括改造免疫细胞以过表达抑制性 ICP 受体的配体，例如程序死亡-1 (PD-1)，或设计融合蛋白，即阿巴西普，结合和抑制参与过度激活的 T 细胞介导的自身免疫的共刺激途径，以及本综述将深入讨论的其他策略。视频摘要。© 2023。作者。

Beyond the encouraging results and broad clinical applicability of immune checkpoint (ICP) inhibitors in cancer therapy, ICP-based immunotherapies in the context of autoimmune disease, particularly multiple sclerosis (MS), have garnered considerable attention and hold great potential for developing effective therapeutic strategies. Given the well-established immunoregulatory role of ICPs in maintaining a balance between stimulatory and inhibitory signaling pathways to promote immune tolerance to self-antigens, a dysregulated expression pattern of ICPs has been observed in a significant proportion of patients with MS and its animal model called experimental autoimmune encephalomyelitis (EAE), which is associated with autoreactivity towards myelin and neurodegeneration. Consequently, there is a rationale for developing immunotherapeutic strategies to induce inhibitory ICPs while suppressing stimulatory ICPs, including engineering immune cells to overexpress ligands for inhibitory ICP receptors, such as program death-1 (PD-1), or designing fusion proteins, namely abatacept, to bind and inhibit the co-stimulatory pathways involved in overactivated T-cell mediated autoimmunity, and other strategies that will be discussed in-depth in the current review. Video Abstract.© 2023. The Author(s).