• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    34031121.pdf
    Size:
    11.30Mb
    Format:
    PDF
    Description:
    From UNPAYWALL
    Download
    Authors
    Pelly, Victoria S
    Moeini, Agrin
    Roelofsen, L. M.
    Bonavita, Eduardo
    Bell, Charlotte R
    Hutton, Colin
    Blanco-Gomez, Adrian
    Banyard, Antonia
    Bromley, Christian P
    Flanagan, Eimear
    Chiang, Shih-Chieh
    Jorgensen, Claus
    Schumacher, T. N.
    Thommen, D
    Zelenay, Santiago
    Show allShow less
    Affiliation
    Cancer Inflammation and Immunity, CRUK Manchester Institute.
    Issue Date
    2021
    
    Metadata
    Show full item record
    Abstract
    Identifying strategies to improve the efficacy of immune checkpoint blockade (ICB) remains a major clinical need. Here, we show that therapeutically targeting the COX-2/PGE2/EP2-4 pathway with widely used non-steroidal and steroidal anti-inflammatory drugs synergized with ICB in mouse cancer models. We exploited a bilateral surgery model to distinguish responders from non-responders shortly following treatment and identified acute IFN-γ-driven transcriptional remodeling in responder mice, which was also associated with patient benefit to ICB. Monotherapy with COX-2 inhibitors or EP2-4 PGE2 receptor antagonists rapidly induced this response program and, in combination with ICB, increased the intratumoral accumulation of effector T cells. Treatment of patient-derived tumor fragments from multiple cancer types revealed a similar shift in the tumor inflammatory environment to favor T cell activation. Our findings establish the COX-2/PGE2/EP2-4 axis as an independent immune checkpoint and a readily translatable strategy to rapidly switch the tumor inflammatory profile from cold to hot.
    Citation
    Pelly VS, Moeini A, Roelofsen LM, Bonavita E, Bell CR, Hutton C, et al. Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy. Cancer Discov. 2021 May 24;candisc.1815.2020.
    Journal
    Cancer Discovery
    URI
    http://hdl.handle.net/10541/624129
    DOI
    10.1158/2159-8290.Cd-20-1815
    PubMed ID
    34031121
    Additional Links
    https://dx.doi.org/10.1158/2159-8290.Cd-20-1815
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1158/2159-8290.Cd-20-1815
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Local and Targeted Delivery of Immune Checkpoint Blockade Therapeutics.
    • Authors: Han X, Li H, Zhou D, Chen Z, Gu Z
    • Issue date: 2020 Nov 17
    • Heterologous prime-boost vaccination targeting MAGE-type antigens promotes tumor T-cell infiltration and improves checkpoint blockade therapy.
    • Authors: McAuliffe J, Chan HF, Noblecourt L, Ramirez-Valdez RA, Pereira-Almeida V, Zhou Y, Pollock E, Cappuccini F, Redchenko I, Hill AV, Leung CSK, Van den Eynde BJ
    • Issue date: 2021 Sep
    • Biomarkers of Immune Checkpoint Blockade Response in Triple-Negative Breast Cancer.
    • Authors: Isaacs J, Anders C, McArthur H, Force J
    • Issue date: 2021 Mar 20
    • Therapeutically Increasing MHC-I Expression Potentiates Immune Checkpoint Blockade.
    • Authors: Gu SS, Zhang W, Wang X, Jiang P, Traugh N, Li Z, Meyer C, Stewig B, Xie Y, Bu X, Manos MP, Font-Tello A, Gjini E, Lako A, Lim K, Conway J, Tewari AK, Zeng Z, Sahu AD, Tokheim C, Weirather JL, Fu J, Zhang Y, Kroger B, Liang JH, Cejas P, Freeman GJ, Rodig S, Long HW, Gewurz BE, Hodi FS, Brown M, Liu XS
    • Issue date: 2021 Jun
    • A bilateral tumor model identifies transcriptional programs associated with patient response to immune checkpoint blockade.
    • Authors: Chen IX, Newcomer K, Pauken KE, Juneja VR, Naxerova K, Wu MW, Pinter M, Sen DR, Singer M, Sharpe AH, Jain RK
    • Issue date: 2020 Sep 22
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.