ArticleScience translational medicine2021
Metabolic regulation by PD-1 signaling promotes long-lived quiescent CD8 T cell memory in mice.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- Spatiotemporal heterologous vaccination relies on type I interferons at priming to enhance mucosal immunity.EMBO molecular medicine · 2026Article
- Siglec-7 orchestrates mitochondrial dynamics and metabolic reprogramming to restrain human NK cell cytotoxic function.The Journal of biological chemistry · 2026Article
- Hypoxia and HIF signalling in tumour microenvironment: linking immune evasion, metabolic rewiring and epigenetic regulation.Expert reviews in molecular medicine · 2026Review
- CCL20-CCR6 signaling alters the metabolic reprogramming to promote the pathogenic Th17 cell differentiation.iScience · 2026Article
- Stem-like T cells: molecular regulation, functional diversity, and therapeutic implications across diseases.Journal of translational medicine · 2025Review
- Life Factors and Melanoma: From the Macroscopic State to the Molecular Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- PD-1 regulates tumor-infiltrating CD8+ T cells in both a cell-intrinsic and a cell-extrinsic fashion.The Journal of experimental medicine · 2025Article
- Depletion of all platelet integrins impacts hemostasis, thrombosis, and tumor metastasis.iScience · 2025Article
- Single-cell RNA sequencing reveals different cellular states in malignant cells and the tumor microenvironment in primary and metastatic ER-positive breast cancer.NPJ breast cancer · 2025Article
- Six degrees of TGFβ.Nature immunology · 2025Article
- Immunometabolism signature derived from on-treatment tumor specimens predicts immune checkpoint blockade response in metastatic melanoma.Discover oncology · 2025Article
- The mechanisms and clinical significance of CD8Cancer biology & medicine · 2025Review
- 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
- A functional single-cell metabolic survey identifies Elovl1 as a target to enhance CD8Nature metabolism · 2025Article
- PD-1 activation mitigates lupus nephritis by suppressing hyperactive and heterogeneous PD-1Theranostics · 2025Article
- Tissue-resident immune cells in cervical cancer: emerging roles and therapeutic implications.Frontiers in immunology · 2025Review
- Siglec-G Suppresses CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Epigenetic tuning of PD-1 expression improves exhausted T cell function and viral control.Nature immunology · 2024Article
- Sustained AhR activity programs memory fate of early effector CD8Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Inhibitory signaling in dysfunctional CD8 T cells through the programmed cell death 1 (PD-1) axis is well established in chronic viral infections and cancers. PD-1 is also transiently induced to high concentrations during priming of acute infections and immunizations, yet its impact on the development of long-lived antigen-independent T cell memory remains unclear. In addition to its expected role in restraining clonal effector expansion, here, we show that PD-1 expression on antigen-specific CD8 T cells is required for the development of a durable CD8 T cell memory pool after antigen clearance. Loss of T cell–specific PD-1 signaling led to increased contraction and a defect in antigen-independent renewal of memory CD8 T cells in response to homeostatic cytokine signals, thus resulting in attrition of the memory pool over time. Whereas exhausted CD8 T cells regain function after PD-1 checkpoint blockade during chronic viral infection, the preexisting pool of resting functional bystander memory CD8 T cells established in response to a previously administered immunogen decreased. Metabolically, PD-1 signals were necessary for regulating the critical balance of mTOR-dependent anabolic glycolysis and fatty acid oxidation programs to meet the bioenergetic needs of quiescent CD8 T cell memory. These results define PD-1 as a key metabolic regulator of protective T cell immunity. Furthermore, these results have potential clinical implications for preexisting CD8 T cell memory during PD-1 checkpoint blockade therapy.
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