ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Programmed death-1 controls T cell survival by regulating oxidative metabolism.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
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Who cites it
80 citing papers in PubMed, 121 citations in OpenAlex.
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- Patient-derived three-dimensional lung tumor models to evaluate response to therapy.NPJ precision oncology · 2026Article
- Correlation Between Oxidative Stress and Immune Profiles During Immunotherapy in Metastatic Non-Oncogene-Addicted NSCLC Patients.Antioxidants (Basel, Switzerland) · 2026Article
- PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling.Cell death & disease · 2026Article
- CAR-T cells in solid tumors: engineering, biomarkers, translational pathways and the road ahead.Frontiers in immunology · 2026Review
- Article
- Modulating the PD-1-FABP5 axis in ILC2s to regulate adipose tissue metabolism in obesity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- DHODH inhibition alters T cell metabolism limiting acute graft-versus-host disease while retaining graft-versus-leukemia response.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Changes in tumor and cardiac metabolism upon immune checkpoint.Basic research in cardiology · 2025Review
- The efficacy and applicability of chimeric antigen receptor (CAR) T cell-based regimens for primary bone tumors: A comprehensive review of current evidence.Journal of bone oncology · 2024Review
- Balanced Duality: HInternational journal of molecular sciences · 2024Review
- T Lymphocyte Characteristic Changes Under Serum Cytokine Deviations and Prognostic Factors of COVID-19 in Pregnant Women.Applied biochemistry and biotechnology · 2024Article
- Unraveling the Role of Reactive Oxygen Species in T Lymphocyte Signaling.International journal of molecular sciences · 2024Review
- Early Initiation of Antiretroviral Therapy Preserves the Metabolic Function of CD4+ T Cells in Subtype C Human Immunodeficiency Virus 1 Infection.The Journal of infectious diseases · 2024Article
- Fatty Acids Play a Critical Role in Mitochondrial Oxidative Phosphorylation in Effector T Cells in Graft-versus-Host Disease.ImmunoHorizons · 2024Article
- The role of ROS in tumor infiltrating immune cells and cancer immunotherapy.Metabolism: clinical and experimental · 2024Review
- Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling.Science advances · 2024Article
- Fatty acid oxidation in immune function.Frontiers in immunology · 2024Review
- Exosomes released from PD-L1Biochemistry and biophysics reports · 2023Article
- Anti-PD-1/Her2 Bispecific Antibody IBI315 Enhances the Treatment Effect of Her2-Positive Gastric Cancer through Gasdermin B-Cleavage Induced Pyroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The coinhibitory receptor programmed death-1 (PD-1) maintains immune homeostasis by negatively regulating T cell function and survival. Blockade of PD-1 increases the severity of graft-versus-host disease (GVHD), but the interplay between PD-1 inhibition and T cell metabolism is not well studied. We found that both murine and human alloreactive T cells concomitantly upregulated PD-1 expression and increased levels of reactive oxygen species (ROS) following allogeneic bone marrow transplantation. This PD-1(Hi)ROS(Hi) phenotype was specific to alloreactive T cells and was not observed in syngeneic T cells during homeostatic proliferation. Blockade of PD-1 signaling decreased both mitochondrial H2O2 and total cellular ROS levels, and PD-1-driven increases in ROS were dependent upon the oxidation of fatty acids, because treatment with etomoxir nullified changes in ROS levels following PD-1 blockade. Downstream of PD-1, elevated ROS levels impaired T cell survival in a process reversed by antioxidants. Furthermore, PD-1-driven changes in ROS were fundamental to establishing a cell's susceptibility to subsequent metabolic inhibition, because blockade of PD-1 decreased the efficacy of later F1F0-ATP synthase modulation. These data indicate that PD-1 facilitates apoptosis in alloreactive T cells by increasing ROS in a process dependent upon the oxidation of fat. In addition, blockade of PD-1 undermines the potential for subsequent metabolic inhibition, an important consideration given the increasing use of anti-PD-1 therapies in the clinic.
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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.