| First Author | Bertrand F | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 2256 |
| PubMed ID | 29273790 | Mgi Jnum | J:259791 |
| Mgi Id | MGI:6112310 | Doi | 10.1038/s41467-017-02358-7 |
| Citation | Bertrand F, et al. (2017) TNFalpha blockade overcomes resistance to anti-PD-1 in experimental melanoma. Nat Commun 8(1):2256 |
| abstractText | 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 alpha (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. |
