IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-23661-4.html
   My bibliography  Save this article

Genetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade

Author

Listed:
  • Zia Khan

    (Genentech)

  • Christian Hammer

    (Genentech)

  • Jonathan Carroll

    (Genentech)

  • Flavia Nucci

    (Genentech)

  • Sergio Ley Acosta

    (Genentech)

  • Vidya Maiya

    (Genentech)

  • Tushar Bhangale

    (Genentech)

  • Julie Hunkapiller

    (Genentech)

  • Ira Mellman

    (Genentech)

  • Matthew L. Albert

    (Genentech
    insitro)

  • Mark I. McCarthy

    (Genentech)

  • G. Scott Chandler

    (F. Hoffmann-La Roche)

Abstract

Activation of systemic immune responses using PD-1 checkpoint inhibitors is an essential approach to cancer therapy. Yet, the extent of benefit relative to risk of immune related adverse events (irAE) varies widely among patients. Here, we study endocrine irAE from 7 clinical trials across 6 cancers where atezolizumab (anti-PD-L1) was combined with chemotherapies and compared to standard of care. We show that atezolizumab-induced thyroid dysfunction is associated with longer survival. We construct a polygenic risk score (PRS) for lifetime risk of hypothyroidism using a GWAS from the UK Biobank and apply this PRS to genetic data collected from 2,616 patients of European ancestry from these trials. Patients with high PRS are at increased risk of atezolizumab-induced thyroid dysfunction and lower risk of death in triple negative breast cancer. Our results indicate that genetic variation associated with thyroid autoimmunity interacts with biological pathways driving the systemic immune response to PD-1 blockade.

Suggested Citation

  • Zia Khan & Christian Hammer & Jonathan Carroll & Flavia Nucci & Sergio Ley Acosta & Vidya Maiya & Tushar Bhangale & Julie Hunkapiller & Ira Mellman & Matthew L. Albert & Mark I. McCarthy & G. Scott Ch, 2021. "Genetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23661-4
    DOI: 10.1038/s41467-021-23661-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-23661-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-23661-4?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. Gunther Glehr & Paloma Riquelme & Katharina Kronenberg & Robert Lohmayer & Víctor J. López-Madrona & Michael Kapinsky & Hans J. Schlitt & Edward K. Geissler & Rainer Spang & Sebastian Haferkamp & Jame, 2024. "Restricting datasets to classifiable samples augments discovery of immune disease biomarkers," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Pooja Middha & Rohit Thummalapalli & Michael J. Betti & Lydia Yao & Zoe Quandt & Karmugi Balaratnam & Cosmin A. Bejan & Eduardo Cardenas & Christina J. Falcon & David M. Faleck & Matthew A. Gubens & S, 2024. "Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis," Nature Communications, Nature, vol. 15(1), pages 1-10, 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:12:y:2021:i:1:d:10.1038_s41467-021-23661-4. 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.