%0 Journal Article
%A Váraljai, Renáta
%A Zimmer, Lisa
%A Al-Matary, Yahya
%A Kaptein, Paulien
%A Albrecht, Lea J
%A Shannan, Batool
%A Brase, Jan C
%A Gusenleitner, Daniel
%A Amaral, Teresa
%A Wyss, Nina
%A Utikal, Jochen
%A Flatz, Lukas
%A Rambow, Florian
%A Reinhardt, Hans Christian
%A Dick, Jenny
%A Engel, Daniel R
%A Horn, Susanne
%A Ugurel, Selma
%A Sondermann, Wiebke
%A Livingstone, Elisabeth
%A Sucker, Antje
%A Paschen, Annette
%A Zhao, Fang
%A Placke, Jan M
%A Klose, Jasmin M
%A Fendler, Wolfgang P
%A Thommen, Daniela S
%A Helfrich, Iris
%A Schadendorf, Dirk
%A Roesch, Alexander
%T Interleukin 17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma.
%J Nature cancer
%V 4
%N 9
%@ 2662-1347
%C London
%I Nature Research
%M DKFZ-2023-01557
%P 1292-1308
%D 2023
%Z 2023 Sep;4(9):1292-1308
%X Recent studies suggest that BRAFV600-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 (TH17) gene expression signatures (GES) in BRAFV600-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-TH17 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 TH17 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37525015
%R 10.1038/s43018-023-00610-2
%U https://inrepo02.dkfz.de/record/277890