ArticlePloS one2014
Blockade of the programmed death-1 (PD1) pathway undermines potent genetic protection from type 1 diabetes.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Successful treatment of nivolumab and ipilimumab triggered type 1 diabetes by using sodium-glucose transporter 2 inhibitor: a case report and systematic review.Frontiers in public health · 2023Pooled it
- PD-1 inhibitor-associated type 1 diabetes: A case report and systematic review.Frontiers in public health · 2022Pooled it
- Murine MHC-Deficient Nonobese Diabetic Mice Carrying Human HLA-DQ8 Develop Severe Myocarditis and Myositis in Response to Anti-PD-1 Immune Checkpoint Inhibitor Cancer Therapy.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Stocking the toolbox-Using preclinical models to understand the development and treatment of immune checkpoint inhibitor-induced immune-related adverse events.Immunological reviews · 2023Review
- Clinical and HLA genotype analysis of immune checkpoint inhibitor-associated diabetes mellitus: a single-center case series from China.Frontiers in immunology · 2023Article
- Immune cells and their inflammatory mediators modify β cells and cause checkpoint inhibitor-induced diabetes.JCI insight · 2022Article
- New-onset type 1 diabetes mellitus as a delayed immune-related event after discontinuation of nivolumab: A case report.Medicine · 2022Article
- Immune checkpoint inhibitor-induced diabetes mellitus with pembrolizumab.BMJ case reports · 2022Article
- Mechanisms and therapeutic strategies of immune checkpoint molecules and regulators in type 1 diabetes.Frontiers in endocrinology · 2022Review
- Characterization of immune checkpoint inhibitor-associated fulminant type 1 diabetes associated with autoantibody status and ethnic origin.Frontiers in immunology · 2022Article
- The side effects of immune checkpoint inhibitor therapy on the endocrine system.The Indian journal of medical research · 2021Review
- Immunotherapy-Associated Pancreatic Adverse Events: Current Understanding of Their Mechanism, Diagnosis, and Management.Frontiers in oncology · 2021Article
- Article
- Cases from the Immune-Related Adverse Event Tumor Board: Diagnosis and Management of Immune Checkpoint Blockade-Induced Diabetes.The oncologist · 2020Article
- Immune checkpoint inhibitor diabetes mellitus: a novel form of autoimmune diabetes.Clinical and experimental immunology · 2020Review
- Article
- The Inhibitory T Cell Receptors PD1 and 2B4 Are Differentially Regulated on CD4 and CD8 T Cells in a Mouse Model of Non-alcoholic Steatohepatitis.Frontiers in pharmacology · 2019Article
- A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity.Journal of autoimmunity · 2018Review
- The Balancing Act between Cancer Immunity and Autoimmunity in Response to Immunotherapy.Cancer immunology research · 2018Review
- Occurrence of type 1 and type 2 diabetes in patients treated with immunotherapy (anti-PD-1 and/or anti-CTLA-4) for metastatic melanoma: a retrospective study.Cancer immunology, immunotherapy : CII · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
aims/hypothesisInhibition of PD1-PDL1 signaling in NOD mice accelerates onset of type 1 diabetes implicating this pathway in suppressing the emergence of pancreatic beta cell reactive T-cells. However, the molecular mechanism by which PD1 signaling protects from type 1 diabetes is not clear. We hypothesized that differential susceptibility of Idd mouse strains to type 1 diabetes when challenged with anti PDL1 will identify genomic loci that collaborate with PD1 signaling in suppressing type 1 diabetes.
methodsAnti PDL1 was administered to NOD and various Idd mouse strains at 10 weeks of age and onset of disease was monitored by measuring blood glucose levels. Additionally, histological evaluation of the pancreas was performed to determine degree of insulitis. Statistical analysis of the data was performed using Log-Rank and Student's t-test.
resultsBlockade of PDL1 rapidly precipitated type 1 diabetes in nearly all NOD Idd congenic strains tested, despite the fact that all are moderately (Idd5, Idd3 and Idd10/18) or highly (Idd3/10/18 and Idd9) protected from spontaneous type 1 diabetes by virtue of their protective Idd genes. Only the Idd3/5 strain, which is nearly 100% protected from spontaneous disease, remained normoglycemic following PDL1 blockade.
conclusionsThese results indicate that multiple Idd loci collaborate with PD1 signaling. Anti PDL1 treatment undermines a large portion of the genetic protection mediated by Idd genes in the NOD model of type 1 diabetes. Basal insulitis correlated with higher susceptibility to type 1 diabetes. These findings have important implications since the PD1 pathway is a target for immunotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.