ArticleScience translational medicine2017
PD-L1 genetic overexpression or pharmacological restoration in hematopoietic stem and progenitor cells reverses autoimmune diabetes.
Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06938334 (A Single-arm, Open-label, Phase I/II Clinical Trial of Autologous Hematopoietic Stem and Progenitor Cells), which is not on this map. Cited by 65 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Single-arm, Open-label, Phase I/II Clinical Trial of Autologous Hematopoietic Stem and Progenitor Cells (HSPCs) Genetically Modified With a Lentiviral Vector (LVV) Encoding for the Human Programmed Death-ligand 1 (hPD-L1) Complementary Deoxyribonucleic Acid (cDNA) for the Treatment of Patients With Type 1 Diabetes (T1D) at Recent Onset and With Residual β-cell Function (IMMUNOSTEM)
Who cites it
65 citing papers in PubMed, 132 citations in OpenAlex.
- Immune checkpoints and immunoregulation in metabolic diseases and cancers: pathological mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2026Review
- Advancing Type 1 Diabetes Treatment: 3 PM-Oriented Innovations in Islet Transplantation and Biomaterial Engineering.Diabetes/metabolism research and reviews · 2026Review
- Stem cell therapies for treatment of diabetes mellitus.Chinese medical journal · 2026Review
- Engineered cell-biomimetic nanosystems for anti-inflammatory therapy: Targeting, neutralization and immunomodulation.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Cell-drug conjugates: a novel drug delivery system for cancer therapy.Theranostics · 2026Review
- Immune modulation for β-cell replacement in type 1 diabetes.Frontiers in immunology · 2026Review
- Single-cell RNA sequencing identifies PD-L1 + mesenchymal stem cells with enhanced immunomodulatory capacity and alleviated the degree of ectopic new bone formation in ankylosing spondylitis.Stem cell research & therapy · 2025Article
- Nanomedicine targeting the PD-1/PD-L1 axis in autoimmune diseases: breaking conventional barriers to restore immune tolerance.Journal of nanobiotechnology · 2025Review
- Advances in Regulatory Cell Therapy for Type 1 Diabetes: Emerging Strategies and Future Directions.European journal of immunology · 2025Review
- Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal.Biological research · 2025Article
- Bioengineering Platelets Presenting PD-L1, Galectin-9 and BTLA to Ameliorate Type 1 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cell-drug conjugates.Nature biomedical engineering · 2024Review
- High glucose-induced injury in human umbilical vein endothelial cells is alleviated by vitamin D supplementation through downregulation of TIPE1.Diabetology & metabolic syndrome · 2024Article
- PD-L1 blockade immunotherapy rewires cancer-induced emergency myelopoiesis.Frontiers in immunology · 2024Article
- Role of EP4 factor in paediatric type 1 diabetes mellitus: a comprehensive review focusing on the honeymoon period.Pediatric endocrinology, diabetes, and metabolism · 2024Review
- An in situ dual-anchoring strategy for enhanced immobilization of PD-L1 to treat autoimmune diseases.Nature communications · 2023Article
- Hydroxyproline metabolism enhances IFN-γ-induced PD-L1 expression and inhibits autophagic flux.Cell chemical biology · 2023Article
- Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Challenges with Cell-based Therapies for Type 1 Diabetes Mellitus.Stem cell reviews and reports · 2023Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 2 countries.
Funding
Abstract
Immunologically based clinical trials performed thus far have failed to cure type 1 diabetes (T1D), in part because these approaches were nonspecific. Because the disease is driven by autoreactive CD4 T cells, which destroy β cells, transplantation of hematopoietic stem and progenitor cells (HSPCs) has been recently offered as a therapy for T1D. Our transcriptomic profiling of HSPCs revealed that these cells are deficient in programmed death ligand 1 (PD-L1), an important immune checkpoint, in the T1D nonobese diabetic (NOD) mouse model. Notably, the immunoregulatory molecule PD-L1 plays a determinant role in controlling/inhibiting activated T cells and thus maintains immune tolerance. Furthermore, our genome-wide and bioinformatic analysis revealed the existence of a network of microRNAs (miRNAs) controlling PD-L1 expression, and silencing one of key altered miRNAs restored PD-L1 expression in HSPCs. We therefore sought to determine whether restoration of this defect would cure T1D as an alternative to immunosuppression. Genetically engineered or pharmacologically modulated HSPCs overexpressing PD-L1 inhibited the autoimmune response in vitro, reverted diabetes in newly hyperglycemic NOD mice in vivo, and homed to the pancreas of hyperglycemic NOD mice. The PD-L1 expression defect was confirmed in human HSPCs in T1D patients as well, and pharmacologically modulated human HSPCs also inhibited the autoimmune response in vitro. Targeting a specific immune checkpoint defect in HSPCs thus may contribute to establishing a cure for T1D.
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What OpenQuestion holds
Registered trials
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.