Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
Clin Exp Immunol. 2020 May;200(2):131-140. doi: 10.1111/cei.13424. Epub 2020 Feb 28.
Autoimmune diabetes mellitus is a rare but significant side effect of treatment with immune checkpoint inhibitors. Immune checkpoint inhibitor-induced diabetes mellitus (CPI-DM) is characterized by acute onset of dramatic hyperglycemia with severe insulin deficiency and occurrence following exposure to programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors rather than cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors. As a growing number of patients undergo immunotherapy, further understanding of the characteristics of CPI-DM patients is needed for improved prognostic and diagnostic application in order to reduce overall morbidity for this already at-risk population. Additionally, understanding of the features and mechanisms of CPI-DM may contribute to understanding mechanisms of spontaneous type I diabetes mellitus (T1DM). Here, we summarize the clinical features of CPI-DM and interrogate the genetic and cellular mechanisms that may contribute to the disease, as well as the clinical challenges for predicting and treating these patients as increasing cancer immunotherapies reach clinical utility.
自身免疫性糖尿病是免疫检查点抑制剂治疗的一种罕见但严重的副作用。免疫检查点抑制剂诱导的糖尿病（CPI-DM）的特征是急性发作、严重高血糖、严重胰岛素缺乏，并在程序性细胞死亡-1/程序性细胞死亡配体-1（PD-1/PD-L1）抑制剂而不是细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）抑制剂暴露后发生。随着越来越多的患者接受免疫治疗，为了降低这一已经处于危险之中的人群的总体发病率，需要进一步了解 CPI-DM 患者的特征，以便在预后和诊断方面有更好的应用。此外，对 CPI-DM 的特征和机制的了解可能有助于理解自发性 1 型糖尿病（T1DM）的机制。在这里，我们总结了 CPI-DM 的临床特征，并探讨了可能导致该疾病的遗传和细胞机制，以及随着越来越多的癌症免疫疗法进入临床应用，预测和治疗这些患者所面临的临床挑战。
