Fiche publication
Date publication
septembre 2023
Journal
Nature cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Dr AMARAL Teresa Maria
Tous les auteurs :
Váraljai R, Zimmer L, Al-Matary Y, Kaptein P, Albrecht LJ, Shannan B, Brase JC, Gusenleitner D, Amaral T, Wyss N, Utikal J, Flatz L, Rambow F, Reinhardt HC, Dick J, Engel DR, Horn S, Ugurel S, Sondermann W, Livingstone E, Sucker A, Paschen A, Zhao F, Placke JM, Klose JM, Fendler WP, Thommen DS, Helfrich I, Schadendorf D, Roesch A
Lien Pubmed
Résumé
Recent studies suggest that BRAF-mutated melanomas in particular respond to dual anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) immune checkpoint inhibition (ICI). Here we identified an over-representation of interleukin (IL)-17-type 17 helper T (T17) gene expression signatures (GES) in BRAF-mutated tumors. Moreover, high baseline IL-17 GES consistently predicted clinical responses in dual-ICI-treated patient cohorts but not in mono anti-CTLA-4 or anti-PD-1 ICI cohorts. High IL-17 GES corresponded to tumor infiltration with T cells and neutrophils. Accordingly, high neutrophil infiltration correlated with clinical response specifically to dual ICI, and tumor-associated neutrophils also showed strong IL-17-T17 pathway activity and T cell activation capacity. Both the blockade of IL-17A and the depletion of neutrophils impaired dual-ICI response and decreased T cell activation. Finally, high IL-17A levels in the blood of patients with melanoma indicated a higher global T17 cytokine profile preceding clinical response to dual ICI but not to anti-PD-1 monotherapy, suggesting a future role as a biomarker for patient stratification.
Mots clés
Humans, Interleukin-17, genetics, CTLA-4 Antigen, metabolism, Programmed Cell Death 1 Receptor, metabolism, Proto-Oncogene Proteins B-raf, therapeutic use, Melanoma, drug therapy
Référence
Nat Cancer. 2023 09;4(9):1292-1308
