2. Academic Validation
  3. TNFα blockade overcomes resistance to anti-PD-1 in experimental melanoma

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

  • Nat Commun. 2017 Dec 22;8(1):2256. doi: 10.1038/s41467-017-02358-7.
Florie Bertrand 1 2,  Anne Montfort 1 2,  Elie Marcheteau 1 2 3 4,  Caroline Imbert 1 2 3 4,  Julia Gilhodes 5,  Thomas Filleron 5,  Philippe Rochaix 5,  Nathalie Andrieu-Abadie 1 2,  Thierry Levade 1 2 3 4 6,  Nicolas Meyer 1 3 4 7,  Céline Colacios 1 2 3 4,  Bruno Ségui 8 9 10 11
Affiliations

Affiliations

  • 1 INSERM UMR 1037, CRCT, 31037, Toulouse, France.
  • 2 Equipe Labellisée Ligue Contre Le Cancer, 31037, Toulouse, France.
  • 3 Université Toulouse III - Paul Sabatier, 31062, Toulouse, France.
  • 4 Université Fédérale de Toulouse Midi-Pyrénées, 41 Allée Jules Guesde, 31000, Toulouse, France.
  • 5 Institut Universitaire du Cancer, 31059, Toulouse, France.
  • 6 Laboratoire de Biochimie, Institut Fédératif de Biologie, CHU Purpan, 31059, Toulouse, France.
  • 7 Institut Universitaire du Cancer, Toulouse, Hôpital Larrey et Oncopôle, 31059, Toulouse, France.
  • 8 INSERM UMR 1037, CRCT, 31037, Toulouse, France. bruno.segui@inserm.fr.
  • 9 Equipe Labellisée Ligue Contre Le Cancer, 31037, Toulouse, France. bruno.segui@inserm.fr.
  • 10 Université Toulouse III - Paul Sabatier, 31062, Toulouse, France. bruno.segui@inserm.fr.
  • 11 Université Fédérale de Toulouse Midi-Pyrénées, 41 Allée Jules Guesde, 31000, Toulouse, France. bruno.segui@inserm.fr.
PMID: 29273790 DOI: 10.1038/s41467-017-02358-7
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.

Figures
Products