IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-23731-7.html
   My bibliography  Save this article

Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade

Author

Listed:
  • Sebastian R. Nielsen

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

  • Jan E. Strøbech

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

  • Edward R. Horton

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

  • Rene Jackstadt

    (CRUK Beatson Institute, Garscube Estate)

  • Anu Laitala

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

  • Marina C. Bravo

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

  • Giorgia Maltese

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

  • Adina R. D. Jensen

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

  • Raphael Reuten

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

  • Maria Rafaeva

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

  • Saadia A. Karim

    (CRUK Beatson Institute, Garscube Estate)

  • Chang-Il Hwang

    (Cold Spring Harbor Laboratory, Cold Spring Harbor
    Lustgarten Pancreatic Cancer Research Laboratory, Cold Spring Harbor
    University of California Davis)

  • Luis Arnes

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

  • David A. Tuveson

    (Cold Spring Harbor Laboratory, Cold Spring Harbor
    Lustgarten Pancreatic Cancer Research Laboratory, Cold Spring Harbor)

  • Owen J. Sansom

    (CRUK Beatson Institute, Garscube Estate
    Institute of Cancer Sciences, University of Glasgow, Garscube Estate)

  • Jennifer P. Morton

    (CRUK Beatson Institute, Garscube Estate
    Institute of Cancer Sciences, University of Glasgow, Garscube Estate)

  • Janine T. Erler

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH))

Abstract

Pancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within the PDAC tumor microenvironment (TME), and are associated with a poor clinical prognosis. However, despite recent advances in understanding neutrophil biology in cancer, therapies targeting tumor-associated neutrophils are lacking. Here, we demonstrate, using pre-clinical mouse models of PDAC, that lorlatinib attenuates PDAC progression by suppressing neutrophil development and mobilization, and by modulating tumor-promoting neutrophil functions within the TME. When combined, lorlatinib also improves the response to anti-PD-1 blockade resulting in more activated CD8 + T cells in PDAC tumors. In summary, this study identifies an effect of lorlatinib in modulating tumor-associated neutrophils, and demonstrates the potential of lorlatinib to treat PDAC.

Suggested Citation

  • Sebastian R. Nielsen & Jan E. Strøbech & Edward R. Horton & Rene Jackstadt & Anu Laitala & Marina C. Bravo & Giorgia Maltese & Adina R. D. Jensen & Raphael Reuten & Maria Rafaeva & Saadia A. Karim & C, 2021. "Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23731-7
    DOI: 10.1038/s41467-021-23731-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-23731-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-23731-7?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. Yanfen Xu & Xi Wang & Yuan Li & Yiheng Mao & Yiran Su & Yize Mao & Yun Yang & Weina Gao & Changying Fu & Wendong Chen & Xueting Ye & Fuchao Liang & Panzhu Bai & Ying Sun & Shengping Li & Ruilian Xu & , 2024. "Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity," Nature Communications, Nature, vol. 15(1), pages 1-18, 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_s41467-021-23731-7. 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.