ArticleCell discovery2019
Global alteration of T-lymphocyte metabolism by PD-L1 checkpoint involves a block of de novo nucleoside phosphate synthesis.
Article in Cell discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Targeting PD-1 post-translational modifications for improving cancer immunotherapy.Cell insight · 2025Review
- Global Trends in Research of Amino Acid Metabolism in T Lymphocytes in Recent 15 Years: A Bibliometric Analysis.Journal of immunology research · 2025Article
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review).Oncology letters · 2024Review
- Expression of the monocarboxylate transporter MCT1 is required for virus-specific mouse CD8Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Plasma Cell Differentiation, Antibody Quality, and Initial Germinal Center B Cell Population Depend on Glucose Influx Rate.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- From multi-omics to predictive biomarker: AI in tumor microenvironment.Frontiers in immunology · 2024Review
- Glucocorticoid dysfunction in children with severe malaria.Frontiers in immunology · 2023Article
- Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment.Frontiers in oncology · 2022Review
- A Compass to Guide Insights into TImmunometabolism · 2022Article
- Bioengineering tools for probing intracellular events in T lymphocytes.WIREs mechanisms of disease · 2021Review
- The Comprehensive "Omics" Approach from Metabolomics to Advanced Omics for Development of Immune Checkpoint Inhibitors: Potential Strategies for Next Generation of Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints.Frontiers in oncology · 2021Review
- The Importance of Metabolism for Immune Homeostasis in Allergic Diseases.Frontiers in immunology · 2021Review
- Determining Factors in the Therapeutic Success of Checkpoint Immunotherapies against PD-L1 in Breast Cancer: A Focus on Epithelial-Mesenchymal Transition Activation.Journal of immunology research · 2021Review
- Amino Acids and Their Transporters in T Cell Immunity and Cancer Therapy.Molecular cell · 2020Review
- CD28 costimulation drives tumor-infiltrating T cell glycolysis to promote inflammation.JCI insight · 2020Article
- Metabolic programming of tumor associated macrophages in the context of cancer treatment.Annals of translational medicine · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Metabolic obstacles of the tumor microenvironment remain a challenge to T-cell-mediated cancer immunotherapies. To better understand the interplay of immune checkpoint signaling and immune metabolism, this study developed and used an optimized metabolite extraction protocol for non-adherent primary human T-cells, to broadly profile in vitro metabolic changes effected by PD-1 signaling by mass spectrometry-based metabolomics and isotopomer analysis. Inhibitory signaling reduced aerobic glycolysis and glutaminolysis. A general scarcity across the panel of metabolites measured supported widespread metabolic regulation by PD-1. Glucose carbon fate analysis supported tricarboxylic acid cycle reliance on pyruvate carboxylation, catabolic-state fluxes into acetyl-CoA and succinyl-CoA, and a block in de novo nucleoside phosphate synthesis that was accompanied by reduced mTORC1 signaling. Nonetheless, exogenous administration of nucleosides was not sufficient to ameliorate proliferation of T-cells in the context of multiple metabolic insufficiencies due to PD-L1 treatment. Carbon fate analysis did not support the use of primarily glucose-derived carbons to fuel fatty acid beta oxidation, in contrast to reports on T-memory cells. These findings add to our understanding of metabolic dysregulation by PD-1 signaling and inform the effort to rationally develop metabolic interventions coupled with immune-checkpoint blockade for increased treatment efficacy.
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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.