ArticleThe Journal of clinical investigation2017
Pyruvate controls the checkpoint inhibitor PD-L1 and suppresses T cell immunity.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Resisting Resistance to Immune Checkpoint Therapy: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Targeting the PD-L1-induced PDK4/GLS metabolic axis overcomes anti-PD-1 resistance in non-small cell lung cancer.Journal for immunotherapy of cancer · 2026Article
- Review
- Progenitor exhausted PD-1Nature cardiovascular research · 2025Article
- Article
- Metabolic Reprogramming in Response to Freund's Adjuvants: Insights from Serum Metabolomics.Microorganisms · 2025Article
- Associations between plasma metabolism-associated proteins and future development of giant cell arteritis: results from a prospective study.Rheumatology (Oxford, England) · 2025Article
- Transmembrane Amino Acid Transporters in Shaping the Metabolic Profile of Breast Cancer Cell Lines: The Focus on Molecular Biological Subtype.Current issues in molecular biology · 2024Review
- Insights into vaccines for elderly individuals: from the impacts of immunosenescence to delivery strategies.NPJ vaccines · 2024Review
- Apolipoproteins and the risk of giant cell arteritis-a nested case-control study.Arthritis research & therapy · 2024Article
- Human dental pulp stem cells modulate pro-inflammatory macrophages both through cell-to-cell contact and paracrine signaling.Frontiers in immunology · 2024Article
- Immune aging - A mechanism in autoimmune disease.Seminars in immunology · 2023Review
- CISH impairs lysosomal function in activated T cells resulting in mitochondrial DNA release and inflammaging.Nature aging · 2023Article
- Deficiency of the CD155-CD96 immune checkpoint controls IL-9 production in giant cell arteritis.Cell reports. Medicine · 2023Article
- Role of Pyruvate Kinase M2 (PKM2) in Cardiovascular Diseases.Journal of cardiovascular translational research · 2023Review
- Lower Frequency of Comorbidities Prior to Onset of Giant Cell Arteritis: A Population-Based Study.The Journal of rheumatology · 2023Article
- CD8Journal of clinical medicine · 2023Article
- BMP4 aggravates mitochondrial dysfunction of HRMECs.Heliyon · 2023Article
- Supplementation with α-ketoglutarate improved the efficacy of anti-PD1 melanoma treatment through epigenetic modulation of PD-L1.Cell death & disease · 2023Article
- Immunology of Giant Cell Arteritis.Circulation research · 2023Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Patients with coronary artery disease (CAD) are at high risk for reactivation of the varicella zoster virus (VZV) and development of herpes zoster (HZ). Here, we found that macrophages from patients with CAD actively suppress T cell activation and expansion, leading to defective VZV-specific T cell immunity. Monocyte-derived and plaque-infiltrating macrophages from patients with CAD spontaneously expressed high surface density of the immunoinhibitory ligand programmed death ligand-1 (PD-L1), thereby providing negative signals to programmed death-1+ (PD-1+) T cells. We determined that aberrant PD-L1 expression in patient-derived macrophages was metabolically controlled. Oversupply of the glycolytic intermediate pyruvate in mitochondria from CAD macrophages promoted expression of PD-L1 via induction of the bone morphogenetic protein 4/phosphorylated SMAD1/5/IFN regulatory factor 1 (BMP4/p-SMAD1/5/IRF1) signaling pathway. Thus, CAD macrophages respond to nutrient excess by activating the immunoinhibitory PD-1/PD-L1 checkpoint, leading to impaired T cell immunity. This finding indicates that metabolite-based immunotherapy may be a potential strategy for restoring adaptive immunity in CAD.
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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.