Journal Article

DKFZ-2023-01557

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Interleukin 17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma.

Váraljai, R.DKFZ* ; Zimmer, L.DKFZ* ; Al-Matary, Y.DKFZ* ; Kaptein, P. ; Albrecht, L. J.DKFZ* ; Shannan, B.DKFZ* ; Brase, J. C. ; Gusenleitner, D. ; Amaral, T. ; Wyss, N. ; Utikal, J.DKFZ* ; Flatz, L. ; Rambow, F.DKFZ* ; Reinhardt, H. C. ; Dick, J. ; Engel, D. R. ; Horn, S.DKFZ* ; Ugurel, S.DKFZ* ; Sondermann, W.DKFZ* ; Livingstone, E.DKFZ* ; Sucker, A.DKFZ* ; Paschen, A.DKFZ* ; Zhao, F.DKFZ* ; Placke, J. M.DKFZ* ; Klose, J. M. ; Fendler, W. P. ; Thommen, D. S. ; Helfrich, I.DKFZ* ; Schadendorf, D.DKFZ* ; Roesch, A.DKFZ*

2023
Nature Research London

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Please use a persistent id in citations: doi:10.1038/s43018-023-00610-2

Abstract: 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.

Note: 2023 Sep;4(9):1292-1308

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)
2. KKE Dermatoonkologie (A370)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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