ArticleProceedings of the National Academy of Sciences of the United States of America2020
Cytocidal macrophages in symbiosis with CD4 and CD8 T cells cause acute diabetes following checkpoint blockade of PD-1 in NOD mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 56 citations in OpenAlex.
- Immune checkpoints and immunoregulation in metabolic diseases and cancers: pathological mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2026Review
- Article
- Immune context governs stage-specific responses to depleting anti-PD-1 antibody in type 1 diabetes.Cell biomaterials · 2026Article
- Review
- Predicting checkpoint inhibitor-associated autoimmune diabetes: prospects and limitations.The Journal of clinical investigation · 2026Article
- Immune checkpoint inhibitor-related endocrinopathies: from immune crosstalk to predictive biomarkers and precision management.Frontiers in endocrinology · 2026Review
- Type 1 diabetes mellitus induced by sintilimab: a case report and related case literature analysis.Frontiers in endocrinology · 2026Review
- Tumor-embedded Immunity and TRM Cell Functions in Cancer.Mini reviews in medicinal chemistry · 2026Review
- An interleukin-27-centered cytokine circuit regulates macrophage and T cell interactions in autoimmune diabetes.iScience · 2025Article
- Adipose-derived mesenchymal stromal/stem cells in type 1 diabetes treatment.Communications biology · 2025Review
- Polyfunctional T follicular helper cells drive checkpoint-inhibitor diabetes and are targeted by JAK inhibitor therapy.JCI insight · 2025Article
- Checkpoint Inhibitor-Induced Autoimmune Diabetes: An Autoinflammatory Disease.Cold Spring Harbor perspectives in medicine · 2025Review
- Gluten-Free Diet Induces Small-Scale Changes Across Multiple T-Cell Subsets in NOD Mice.European journal of immunology · 2025Article
- Tissue Resident and Infiltrating Immune Cells: Their Influence on the Demise of Beta Cells in Type 1 Diabetes.Biomolecules · 2025Review
- Type I Diabetes-A Rare Adverse Event Described in Patients Receiving Immunotherapy Versus a Side Effect from SARS-CoV-2 Infection.Reports (MDPI) · 2025Article
- Cemiplimab and diabetic ketoacidosis: a case report of a rare endocrinopathy associated with immune checkpoint inhibitors.Frontiers in endocrinology · 2025Article
- Autoimmune CD4Immunity · 2024Article
- TGF-β-mediated crosstalk between TIGITNature communications · 2024Article
- CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8Immunity · 2024Article
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Autoimmune diabetes is one of the complications resulting from checkpoint blockade immunotherapy in cancer patients, yet the underlying mechanisms for such an adverse effect are not well understood. Leveraging the diabetes-susceptible nonobese diabetic (NOD) mouse model, we phenocopy the diabetes progression induced by programmed death 1 (PD-1)/PD-L1 blockade and identify a cascade of highly interdependent cellular interactions involving diabetogenic CD4 and CD8 T cells and macrophages. We demonstrate that exhausted CD8 T cells are the major cells that respond to PD-1 blockade producing high levels of IFN-γ. Most importantly, the activated T cells lead to the recruitment of monocyte-derived macrophages that become highly activated when responding to IFN-γ. These macrophages acquire cytocidal activity against β-cells via nitric oxide and induce autoimmune diabetes. Collectively, the data in this study reveal a critical role of macrophages in the PD-1 blockade-induced diabetogenesis, providing new insights for the understanding of checkpoint blockade immunotherapy in cancer and infectious diseases.
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