%0 Journal Article
%A Denk, Dominic
%A Ramakrishnan, Mallika
%A Conche, Claire
%A Pallangyo, Charles
%A Pesic, Marina
%A Ceteci, Fatih
%A Kennel, Kilian B
%A Kirisözü, Asude C
%A Engel, Esther
%A Mohs, Kathleen
%A Ritter, Birgit
%A Pardo, Angeles Macias
%A Özkurt, Ezgi
%A Hildebrand, Falk
%A Waisman, Ari
%A Arkan, Melek C
%A Greten, Florian R
%T IL-17RA signaling provides dual tumor-suppressor function during late-stage colorectal carcinogenesis.
%J Immunity
%V 58
%N 3
%@ 1074-7613
%C [Cambridge, Mass.]
%I Cell Press
%M DKFZ-2025-00469
%P 701-715.e8
%D 2025
%Z 2025 Mar 11;58(3):701-715.e8
%X Expression of interleukin (IL)-17 family cytokines is associated with tumor-promoting inflammation. We found that low expression of IL17RA associated with worse prognosis in late-stage colorectal cancer (CRC) patients. Deletion of Il17ra in intestinal epithelial cells (IECs) in a murine model of CRC enhanced epithelial-to-mesenchymal transition (EMT) via increased expression of the epidermal growth factor receptor and subsequent activation of the kinase Src. Yet, these mice were protected from metastatic disease; Il17ra deletion impaired intestinal barrier function and enhanced systemic fungal invasion and associated immunity. However, in macrophages, IL-17RA was required for spleen tyrosine kinase (Syk) activation upon fungal-induced dectin-1 engagement, and Il17ra ablation impaired IL-18 release and protective CD8+ T cell-mediated anti-tumor immunity. Combining recombinant IL-17 and heat-killed Candida albicans rendered colorectal tumors sensitive to α-PD-1 treatment in a model of microsatellite stable (MSS) CRC. Thus, IL-17RA engages two distinct tumor-suppressive mechanisms in CRC, linking EMT and fungal-induced anti-tumor immunity during tumor progression.
%K CRC (Other)
%K EMT (Other)
%K IL-17 (Other)
%K IL-17RA (Other)
%K anti-tumor immunity (Other)
%K colon cancer (Other)
%K immunotherapy (Other)
%K inflammation (Other)
%K mycobiome (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40023157
%R 10.1016/j.immuni.2025.02.005
%U https://inrepo02.dkfz.de/record/299511