IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7692.html
   My bibliography  Save this article

PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation

Author

Listed:
  • Nikolaos Patsoukis

    (Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Cancer Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Kankana Bardhan

    (Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Cancer Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Pranam Chatterjee

    (Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Cancer Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Duygu Sari

    (Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Cancer Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Bianling Liu

    (Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Cancer Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Lauren N. Bell

    (Metabolon, Inc.)

  • Edward D. Karoly

    (Metabolon, Inc.)

  • Gordon J. Freeman

    (Dana-Farber Cancer Institute)

  • Victoria Petkova

    (Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Cancer Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Pankaj Seth

    (Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Cancer Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Medical Centerr, Harvard Medical School, 330 Brookline Avenue, Dana 513-517, Boston, Massachusetts 02215, USA)

  • Lequn Li

    (Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Cancer Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Vassiliki A. Boussiotis

    (Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Beth Israel Deaconess Cancer Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

Abstract

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.

Suggested Citation

  • Nikolaos Patsoukis & Kankana Bardhan & Pranam Chatterjee & Duygu Sari & Bianling Liu & Lauren N. Bell & Edward D. Karoly & Gordon J. Freeman & Victoria Petkova & Pankaj Seth & Lequn Li & Vassiliki A. , 2015. "PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7692
    DOI: 10.1038/ncomms7692
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7692
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7692?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Theinmozhi Arulraj & Debashis Barik, 2018. "Mathematical modeling identifies Lck as a potential mediator for PD-1 induced inhibition of early TCR signaling," PLOS ONE, Public Library of Science, vol. 13(10), pages 1-23, October.
    2. Jacqueline A. Turner & Malia A. Fredrickson & Marc D’Antonio & Elizabeth Katsnelson & Morgan MacBeth & Robert Gulick & Tugs-Saikhan Chimed & Martin McCarter & Angelo D’Alessandro & William A. Robinson, 2023. "Lysophosphatidic acid modulates CD8 T cell immunosurveillance and metabolism to impair anti-tumor immunity," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7692. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.