IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-02358-7.html
   My bibliography  Save this article

TNFα blockade overcomes resistance to anti-PD-1 in experimental melanoma

Author

Listed:
  • Florie Bertrand

    (INSERM UMR 1037, CRCT
    Equipe Labellisée Ligue Contre Le Cancer)

  • Anne Montfort

    (INSERM UMR 1037, CRCT
    Equipe Labellisée Ligue Contre Le Cancer)

  • Elie Marcheteau

    (INSERM UMR 1037, CRCT
    Equipe Labellisée Ligue Contre Le Cancer
    Université Toulouse III - Paul Sabatier
    Université Fédérale de Toulouse Midi-Pyrénées)

  • Caroline Imbert

    (INSERM UMR 1037, CRCT
    Equipe Labellisée Ligue Contre Le Cancer
    Université Toulouse III - Paul Sabatier
    Université Fédérale de Toulouse Midi-Pyrénées)

  • Julia Gilhodes

    (Institut Universitaire du Cancer)

  • Thomas Filleron

    (Institut Universitaire du Cancer)

  • Philippe Rochaix

    (Institut Universitaire du Cancer)

  • Nathalie Andrieu-Abadie

    (INSERM UMR 1037, CRCT
    Equipe Labellisée Ligue Contre Le Cancer)

  • Thierry Levade

    (INSERM UMR 1037, CRCT
    Equipe Labellisée Ligue Contre Le Cancer
    Université Toulouse III - Paul Sabatier
    Université Fédérale de Toulouse Midi-Pyrénées)

  • Nicolas Meyer

    (INSERM UMR 1037, CRCT
    Université Toulouse III - Paul Sabatier
    Université Fédérale de Toulouse Midi-Pyrénées
    Toulouse, Hôpital Larrey et Oncopôle)

  • Céline Colacios

    (INSERM UMR 1037, CRCT
    Equipe Labellisée Ligue Contre Le Cancer
    Université Toulouse III - Paul Sabatier
    Université Fédérale de Toulouse Midi-Pyrénées)

  • Bruno Ségui

    (INSERM UMR 1037, CRCT
    Equipe Labellisée Ligue Contre Le Cancer
    Université Toulouse III - Paul Sabatier
    Université Fédérale de Toulouse Midi-Pyrénées)

Abstract

Antibodies against programmed cell death-1 (PD-1) have considerably changed the treatment for melanoma. However, many patients do not display therapeutic response or eventually relapse. Moreover, patients treated with anti-PD-1 develop immune-related adverse events that can be cured with anti-tumor necrosis factor α (TNF) antibodies. Whether anti-TNF antibodies affect the anti-cancer immune response remains unknown. Our recent work has highlighted that TNFR1-dependent TNF signalling impairs the accumulation of CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) in mouse melanoma. Herein, our results indicate that TNF or TNFR1 blockade synergizes with anti-PD-1 on anti-cancer immune responses towards solid cancers. Mechanistically, TNF blockade prevents anti-PD-1-induced TIL cell death as well as PD-L1 and TIM-3 expression. TNF expression positively correlates with expression of PD-L1 and TIM-3 in human melanoma specimens. This study provides a strong rationale to develop a combination therapy based on the use of anti-PD-1 and anti-TNF in cancer patients.

Suggested Citation

  • Florie Bertrand & Anne Montfort & Elie Marcheteau & Caroline Imbert & Julia Gilhodes & Thomas Filleron & Philippe Rochaix & Nathalie Andrieu-Abadie & Thierry Levade & Nicolas Meyer & Céline Colacios &, 2017. "TNFα blockade overcomes resistance to anti-PD-1 in experimental melanoma," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02358-7
    DOI: 10.1038/s41467-017-02358-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-02358-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-02358-7?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. Paul K. Paik & Jia Luo & Ni Ai & Rachel Kim & Linda Ahn & Anup Biswas & Courtney Coker & Wanchao Ma & Phillip Wong & Darren J. Buonocore & W. Victoria Lai & Jamie E. Chaft & Swarnali Acharyya & Joan M, 2022. "Phase I trial of the TNF-α inhibitor certolizumab plus chemotherapy in stage IV lung adenocarcinomas," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    2. Timothy R. McCulloch & Gustavo R. Rossi & Louisa Alim & Pui Yeng Lam & Joshua K. M. Wong & Elaina Coleborn & Snehlata Kumari & Colm Keane & Andrew J. Kueh & Marco J. Herold & Christoph Wilhelm & Percy, 2024. "Dichotomous outcomes of TNFR1 and TNFR2 signaling in NK cell-mediated immune responses during inflammation," Nature Communications, Nature, vol. 15(1), pages 1-16, 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_s41467-017-02358-7. 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.