IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms14649.html
   My bibliography  Save this article

Suppressive IL-17A+Foxp3+ and ex-Th17 IL-17AnegFoxp3+ Treg cells are a source of tumour-associated Treg cells

Author

Listed:
  • Stephanie Downs-Canner

    (University of Pittsburgh)

  • Sara Berkey

    (University of Pittsburgh)

  • Greg M. Delgoffe

    (University of Pittsburgh Cancer Institute
    Tumour Microenvironment Center, Hillman Cancer Center, University of Pittsburgh
    Magee-Womens Research Institute Ovarian Cancer Center of Excellence)

  • Robert P. Edwards

    (University of Pittsburgh Cancer Institute
    Magee-Womens Research Institute Ovarian Cancer Center of Excellence
    Peritoneal/Ovarian Cancer Specialty Care Center)

  • Tyler Curiel

    (UT Health Science Center at San Antonio)

  • Kunle Odunsi

    (Roswell Park Cancer Institute)

  • David L. Bartlett

    (University of Pittsburgh)

  • Nataša Obermajer

    (University of Pittsburgh)

Abstract

Th17 and regulatory T (Treg) cells are integral in maintaining immune homeostasis and Th17–Treg imbalance is associated with inflammatory immunosuppression in cancer. Here we show that Th17 cells are a source of tumour-induced Foxp3+ cells. In addition to natural (n)Treg and induced (i)Treg cells that develop from naive precursors, suppressive IL-17A+Foxp3+ and ex-Th17 Foxp3+ cells are converted from IL-17A+Foxp3neg cells in tumour-bearing mice. Metabolic phenotyping of Foxp3-expressing IL-17A+, ex-Th17 and iTreg cells demonstrates the dissociation between the metabolic fitness and the suppressive function of Foxp3-expressing Treg cell subsets. Although all Foxp3-expressing subsets are immunosuppressive, glycolysis is a prominent metabolic pathway exerted only by IL-17A+Foxp3+ cells. Transcriptome analysis and flow cytometry of IL-17A+Foxp3+ cells indicate that Folr4, GARP, Itgb8, Pglyrp1, Il1rl1, Itgae, TIGIT and ICOS are Th17-to-Treg cell transdifferentiation-associated markers. Tumour-associated Th17-to-Treg cell conversion identified here provides insights for targeting the dynamism of Th17–Treg cells in cancer immunotherapy.

Suggested Citation

  • Stephanie Downs-Canner & Sara Berkey & Greg M. Delgoffe & Robert P. Edwards & Tyler Curiel & Kunle Odunsi & David L. Bartlett & Nataša Obermajer, 2017. "Suppressive IL-17A+Foxp3+ and ex-Th17 IL-17AnegFoxp3+ Treg cells are a source of tumour-associated Treg cells," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14649
    DOI: 10.1038/ncomms14649
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms14649
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms14649?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
    ---><---

    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:8:y:2017:i:1:d:10.1038_ncomms14649. 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.