Establishment of the prediction of type I diabetes mellitus onset in the patient administered immune checkpoint inhibitor.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18007
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Osaka University
• Principal Investigator: Fujita Yukari 大阪大学, 医学系研究科, 寄附講座助教 (60837003)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: PD-L1の発現

Outline of Final Research Achievements

Pancreatic tissues from 3 patients who developed type 1 diabetes after PD-1 antibody treatment (T1D), 3 patients who did not develop type 1 diabetes despite PD-1 antibody treatment (non-T1D), and 7 patients with normal glucose tolerance (control) were used to compare pancreatic beta cell volume, islet inflammation, and PD-L1 expression. Pancreatic β-cell volume was markedly decreased in T1D. Insulitis was observed in T1D and non-T1D, but not in control. PD-L1 expression in pancreatic β-cells was markedly decreased in the PD-1 antibody-treated patients (T1D and non-T1D).
The results suggest that PD-L1 expression in pancreatic beta cells is decreased by PD-1 antibody treatment, resulting in insulitis, but other factors may be involved in whether or not type 1 diabetes develops.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

PD-1抗体の投与により、1型糖尿病非発症者においても膵β細胞のPD-L1発現が低下していることが明らかとなった。ICI関連糖尿病の最大の原因であると考えられ、PD-1抗体を投与される患者では全ての患者が1型糖尿病発症の可能性を念頭に置く必要がある。