Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
The Second Clinical Medicine School, Nanchang University, Nanchang, China.
Front Endocrinol (Lausanne). 2023 Jan 10;13:1090842. doi: 10.3389/fendo.2022.1090842. eCollection 2022.
Considered a significant risk to health and survival, type 1 diabetes (T1D) is a heterogeneous autoimmune disease characterized by hyperglycemia caused by an absolute deficiency of insulin, which is mainly due to the immune-mediated destruction of pancreatic beta cells.
In recent years, the role of immune checkpoints in the treatment of cancer has been increasingly recognized, but unfortunately, little attention has been paid to the significant role they play both in the development of secondary diabetes with immune checkpoint inhibitors and the treatment of T1D, such as cytotoxic T-lymphocyte antigen 4(CTLA-4), programmed cell death protein-1(PD-1), lymphocyte activation gene-3(LAG-3), programmed death ligand-1(PD-L1), and T-cell immunoglobulin mucin protein-3(TIM-3). Here, this review summarizes recent research on the role and mechanisms of diverse immune checkpoint molecules in mediating the development of T1D and their potential and theoretical basis for the prevention and treatment of diabetes.
Immune checkpoint inhibitors related diabetes, similar to T1D, are severe endocrine toxicity induced with immune checkpoint inhibitors. Interestingly, numerous treatment measures show excellent efficacy for T1D regulating diverse immune checkpoint molecules, including co-inhibitory and co-stimulatory molecules. Thus, targeting immune checkpoint molecules may exhibit potential for T1D treatment and improve clinical outcomes.
1 型糖尿病（T1D）被认为是对健康和生存的重大威胁，是一种异质性自身免疫性疾病，其特征是由于胰岛素绝对缺乏导致的高血糖，主要是由于免疫介导的胰腺β细胞破坏。
近年来，免疫检查点在癌症治疗中的作用越来越受到重视，但令人遗憾的是，人们对它们在免疫检查点抑制剂引起的继发性糖尿病和 T1D 治疗中的重要作用几乎没有关注，如细胞毒性 T 淋巴细胞抗原 4（CTLA-4）、程序性细胞死亡蛋白-1（PD-1）、淋巴细胞激活基因-3（LAG-3）、程序性死亡配体-1（PD-L1）和 T 细胞免疫球蛋白粘蛋白蛋白-3（TIM-3）。本文总结了近年来关于不同免疫检查点分子在介导 T1D 发生发展中的作用及其在预防和治疗糖尿病方面的潜在和理论基础的研究进展。
免疫检查点抑制剂相关糖尿病与 T1D 相似，是免疫检查点抑制剂引起的严重内分泌毒性。有趣的是，许多治疗措施对 T1D 的调节显示出对多种免疫检查点分子的优异疗效，包括共抑制和共刺激分子。因此，靶向免疫检查点分子可能为 T1D 的治疗提供潜力，并改善临床结局。
