TY  - JOUR
AU  - Denk, Dominic
AU  - Ramakrishnan, Mallika
AU  - Conche, Claire
AU  - Pallangyo, Charles
AU  - Pesic, Marina
AU  - Ceteci, Fatih
AU  - Kennel, Kilian B
AU  - Kirisözü, Asude C
AU  - Engel, Esther
AU  - Mohs, Kathleen
AU  - Ritter, Birgit
AU  - Pardo, Angeles Macias
AU  - Özkurt, Ezgi
AU  - Hildebrand, Falk
AU  - Waisman, Ari
AU  - Arkan, Melek C
AU  - Greten, Florian R
TI  - IL-17RA signaling provides dual tumor-suppressor function during late-stage colorectal carcinogenesis.
JO  - Immunity
VL  - 58
IS  - 3
SN  - 1074-7613
CY  - [Cambridge, Mass.]
PB  - Cell Press
M1  - DKFZ-2025-00469
SP  - 701-715.e8
PY  - 2025
N1  - 2025 Mar 11;58(3):701-715.e8
AB  - 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.
KW  - CRC (Other)
KW  - EMT (Other)
KW  - IL-17 (Other)
KW  - IL-17RA (Other)
KW  - anti-tumor immunity (Other)
KW  - colon cancer (Other)
KW  - immunotherapy (Other)
KW  - inflammation (Other)
KW  - mycobiome (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40023157
DO  - DOI:10.1016/j.immuni.2025.02.005
UR  - https://inrepo02.dkfz.de/record/299511
ER  -