Unraveling the role of stromal IL-36R signaling in colorectal tumorigenesis
Project Leaders
Dr. Kristina Koop
FAU Erlangen-Nürnberg
Research Focus
The IL-36 cytokine family is a pro-inflammatory member of the IL-1 family that plays a significant role in inflammatory bowel diseases and is predominantly expressed by immune cells and stromal cells. P09's goal is to understand how IL-36 receptor signaling affects cancer-associated fibroblasts (CAFs) and tumor-infiltrating T cells in the tumor microenvironment and thereby the project will determine the functional relevance of IL-36R signaling in vitro and in vivo. In particular, the project will take advantage of genetic mouse models and human tissue as well as a human tumor organoid co-culture model. This will help to determine whether IL-36 can limit tumor growth and whether IL-36 signaling can be targeted in colorectal carcinoma (CRC).
Main Collaborations
- P01 Greten: Modulating CAF plasticity to enable immunotherapy of colorectal cancer:
- P04 Farin/Stemmler: Mapping the CAF subtype-dependent reciprocal signaling in the CRC niche:
- P08 Weigert: The role of IL-38 in shaping tumor-promoting versus protective inflammation in colorectal cancer:
- P14 Kesselring/Minguet: The role of γδ T cells in the tumor microenvironment of colorectal cancer:
- P18 Buchholz/Farin: Identifying and overcoming CAR T cell barriers in the colorectal carcinoma microenvironment:
- S01 Berlin/Greten/Naschberger: Human tumor organoid biobanks for preclinical validation:
- S02 Reiss/Ritter: Spatial profiling of the tumor microenvironment in CRC:
- S03 Börries/Gupta: Research information infrastructure, data management and bioinformatics core:
Publications
Pathophysiology of colitis-associated colorectal cancer
Neufert C, Neurath MF.
Nat Rev Gastroenterol Hepatol. 2026 Jul;23(7):549-562. doi: 10.1038/s41575-026-01197-6. Epub 2026 Apr 1. PMID: 41922722.
The endogenous peptide GPR15L shapes the intestinal microbiota to counteract colitis
Leggio M, Schramm S, Dietz L, Ocón B, Wirtz S, Puertolas Balint F, Yilmaz B, Petzold J, Liu LJ, Dedden M, Ekici A; TRR241 IBDome Consortium; Meng X, Bingham D, Ullrich KA, Heltmann-Meyer S, Günther C, Hildner K, Atreya R, Atreya I, Müller TM, Gerlach RG, Schroeder BO, Macpherson A, Butcher EC, Neurath MF, Zundler S; TRR241 IBCome Consortium.
Gut. 2026 Jun 25:gutjnl-2025-337619. doi: 10.1136/gutjnl-2025-337619. Epub ahead of print. PMID: 42209192.
Interleukin 36 receptor-inducible matrix metalloproteinase 13 mediates intestinal fibrosis
Koop K, Enderle K, Hillmann M, Ruspeckhofer L, Vieth M, Sturm G, Trajanoski Z, Kühl AA, Atreya R, Leppkes M, Baum P, Roy J, Martin A, Neurath MF, Neufert C.
Front Immunol. 2023 May 3;14:1163198. doi: 10.3389/fimmu.2023.1163198. eCollection 2023. PMID: 37207229
IL-36 in chronic inflammation and cancer
Neurath MF.
Cytokine Growth Factor Rev. 2020 Oct;55:70-79. doi: 10.1016/j.cytogfr.2020.06.006. Epub 2020 Jun 7. PMID: 32540133
IL-36R signalling activates intestinal epithelial cells and fibroblasts and promotes mucosal healing in vivo
Scheibe K, Backert I, Wirtz S, Hueber A, Schett G, Vieth M, Probst HC, Bopp T, Neurath MF, Neufert C.
Gut. 2017 May;66(5):823-838. doi: 10.1136/gutjnl-2015-310374. Epub 2016 Jan 18. PMID: 26783184
Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer
Punkenburg E, Vogler T, Büttner M, Amann K, Waldner M, Atreya R, Abendroth B, Mudter J, Merkel S, Gallmeier E, Rose-John S, Neurath MF, Hildner K.
Gut. 2016 Jul;65(7):1139-50. doi: 10.1136/gutjnl-2014-308227. Epub 2015 Apr 2. PMID: 25838550