The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation
Open accessAbstract
During activation, T cells undergo metabolic reprogramming, which imprints distinct functional fates. We determined that on PD-1 ligation, activated T cells are unable to engage in glycolysis or amino acid metabolism but have an increased rate of fatty acid β-oxidation (FAO). PD-1 promotes FAO of endogenous lipids by increasing expression of CPT1A, and inducing lipolysis as indicated by elevation of the lipase ATGL, the lipolysis marker glycerol and release of fatty acids. Conversely, CTLA-4 inhibits glycolysis without augmenting FAO, suggesting that CTLA-4 sustains the metabolic profile of non-activated cells. Because T cells utilize glycolysis during differentiation to effectors, our findings reveal a metabolic mechanism responsible for PD-1-mediated blockade of T-effector cell differentiation. The enhancement of FAO provides a mechanistic explanation for the longevity of T cells receiving PD-1 signals in patients with chronic infections and cancer, and for their capacity to be reinvigorated by PD-1 blockade.
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Cites
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PD-L2 is a second ligand for PD-1 and inhibits T cell activation
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Self-citationPD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
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The CD28 Signaling Pathway Regulates Glucose Metabolism
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CTLA-4: new insights into its biological function and use in tumor immunotherapy
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A guide to immunometabolism for immunologists
O'Neill, L. A. J., Kishton, R. J., & Rathmell, J. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.70 · Cited by 3,315
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy
Wei, S. C., Duffy, C. R., & Allison, J. P. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0367 · Cited by 3,088
Cytotoxic CD8+ T cells in cancer and cancer immunotherapy
Raskov, H., Orhan, A., Christensen, J. P., & Gögenur, I. (2021) · British Journal of Cancer · doi:10.1038/s41416-020-01048-4 · Cited by 1,687
The cancer metabolic reprogramming and immune response
Xia, L., Oyang, L., Lin, J., Tan, S., Han, Y., Wu, N., Yi, P., Tang, L., Pan, Q., Rao, S., et al. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01316-8 · Cited by 1,312
Metadata
- Authors
- Patsoukis, N., Bardhan, K., Chatterjee, P., Sari, D., Liu, B., Bell, L. N., Karoly, E. D., Freeman, G. J., Petkova, V., Seth, P., Li, L., & Boussiotis, V. A.
- Venue
- Nature Communications
- Published
- 2015-03-26
- Volume
- 6
- Issue
- 1
- Pages
- 6692-6692
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W1993686673
- Cited by
- 1,202
- References
- 13
- FWCI
- 29.13
- Type
- journal article
- Language
- en
- Open access
- gold
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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