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@ARTICLE{Denk:299511,
author = {D. Denk and M. Ramakrishnan and C. Conche and C. Pallangyo
and M. Pesic and F. Ceteci and K. B. Kennel and A. C.
Kirisözü and E. Engel and K. Mohs and B. Ritter and A. M.
Pardo and E. Özkurt and F. Hildebrand and A. Waisman and M.
C. Arkan$^*$ and F. R. Greten$^*$},
title = {{IL}-17{RA} signaling provides dual tumor-suppressor
function during late-stage colorectal carcinogenesis.},
journal = {Immunity},
volume = {58},
number = {3},
issn = {1074-7613},
address = {[Cambridge, Mass.]},
publisher = {Cell Press},
reportid = {DKFZ-2025-00469},
pages = {701-715.e8},
year = {2025},
note = {2025 Mar 11;58(3):701-715.e8},
abstract = {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.},
keywords = {CRC (Other) / EMT (Other) / IL-17 (Other) / IL-17RA (Other)
/ anti-tumor immunity (Other) / colon cancer (Other) /
immunotherapy (Other) / inflammation (Other) / mycobiome
(Other)},
cin = {FM01},
ddc = {610},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40023157},
doi = {10.1016/j.immuni.2025.02.005},
url = {https://inrepo02.dkfz.de/record/299511},
}