IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-01883-9.html
   My bibliography  Save this article

DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells

Author

Listed:
  • Hiro Sato

    (Gunma University Graduate School of Medicine)

  • Atsuko Niimi

    (Gunma University Initiative for Advanced Research (GIAR))

  • Takaaki Yasuhara

    (The University of Tokyo)

  • Tiara Bunga Mayang Permata

    (Gunma University Graduate School of Medicine)

  • Yoshihiko Hagiwara

    (Gunma University Graduate School of Medicine)

  • Mayu Isono

    (Gunma University)

  • Endang Nuryadi

    (Gunma University Graduate School of Medicine)

  • Ryota Sekine

    (Gunma University)

  • Takahiro Oike

    (Gunma University Graduate School of Medicine)

  • Sangeeta Kakoti

    (Gunma University Graduate School of Medicine)

  • Yuya Yoshimoto

    (Gunma University Graduate School of Medicine)

  • Kathryn D. Held

    (Massachusetts General Hospital/Harvard Medical School
    Gunma University Initiative for Advanced Research (GIAR))

  • Yoshiyuki Suzuki

    (Fukushima Medical University)

  • Koji Kono

    (Fukushima Medical University)

  • Kiyoshi Miyagawa

    (The University of Tokyo)

  • Takashi Nakano

    (Gunma University Graduate School of Medicine
    Gunma University Initiative for Advanced Research (GIAR))

  • Atsushi Shibata

    (Gunma University
    Graduate School of Medicine, Gunma University)

Abstract

Accumulating evidence suggests that exogenous cellular stress induces PD-L1 upregulation in cancer. A DNA double-strand break (DSB) is the most critical type of genotoxic stress, but the involvement of DSB repair in PD-L1 expression has not been investigated. Here we show that PD-L1 expression in cancer cells is upregulated in response to DSBs. This upregulation requires ATM/ATR/Chk1 kinases. Using an siRNA library targeting DSB repair genes, we discover that BRCA2 depletion enhances Chk1-dependent PD-L1 upregulation after X-rays or PARP inhibition. In addition, we show that Ku70/80 depletion substantially enhances PD-L1 upregulation after X-rays. The upregulation by Ku80 depletion requires Chk1 activation following DNA end-resection by Exonuclease 1. DSBs activate STAT1 and STAT3 signalling, and IRF1 is required for DSB-dependent PD-L1 upregulation. Thus, our findings reveal the involvement of DSB repair in PD-L1 expression and provide mechanistic insight into how PD-L1 expression is regulated after DSBs.

Suggested Citation

  • Hiro Sato & Atsuko Niimi & Takaaki Yasuhara & Tiara Bunga Mayang Permata & Yoshihiko Hagiwara & Mayu Isono & Endang Nuryadi & Ryota Sekine & Takahiro Oike & Sangeeta Kakoti & Yuya Yoshimoto & Kathryn , 2017. "DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01883-9
    DOI: 10.1038/s41467-017-01883-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-01883-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-01883-9?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. I.-M. Launonen & N. Lyytikäinen & J. Casado & E. A. Anttila & A. Szabó & U.-M. Haltia & C. A. Jacobson & J. R. Lin & Z. Maliga & B. E. Howitt & K. C. Strickland & S. Santagata & K. Elias & A. D. D’And, 2022. "Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Elizabeth L. Hardaker & Emilio Sanseviero & Ankur Karmokar & Devon Taylor & Marta Milo & Chrysis Michaloglou & Adina Hughes & Mimi Mai & Matthew King & Anisha Solanki & Lukasz Magiera & Ricardo Miraga, 2024. "The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-20, 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:8:y:2017:i:1:d:10.1038_s41467-017-01883-9. 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.