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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
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    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.

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