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

Florie Bertrand, Anne Montfort, Elie Marcheteau, Caroline Imbert, Julia Gilhodes, Thomas Filleron, Philippe Rochaix, Nathalie Andrieu-Abadie, Thierry Levade, Nicolas Meyer, Céline Colacios and Bruno Ségui ()
Additional contact information
Florie Bertrand: INSERM UMR 1037, CRCT
Anne Montfort: INSERM UMR 1037, CRCT
Elie Marcheteau: INSERM UMR 1037, CRCT
Caroline Imbert: INSERM UMR 1037, CRCT
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
Thierry Levade: INSERM UMR 1037, CRCT
Nicolas Meyer: INSERM UMR 1037, CRCT
Céline Colacios: INSERM UMR 1037, CRCT
Bruno Ségui: INSERM UMR 1037, CRCT

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02358-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02358-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02358-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().