The role of LIFR signaling in CAFs in CRC
Project Leader
Research Focus
P05 developed a comprehensive research program to decipher the exact role of LIF signaling in colorectal CAFs and its role in driving tumor expansion and metastasis. Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that belongs to the IL-6 superfamily and which activates JAK/STAT3 as well as PI3K/AKT, ERK1/2 and mTOR signaling. LIF and LIFR expression will be determined in different molecular CRC subtypes and in vivo relevance will be evaluated using genetic models in primary tumors and metastases as well as by orthotopic transplantation of human tumor organoids in a humanized mouse model.
Main Collaborations
- P01 Greten: Modulating CAF plasticity to enable immunotherapy of colorectal cancer:
- P03 Briquez/Fichtner-Feigl/Reuten: Metastasis predisposing extracellular matrix architecture in colorectal cancer:
- P04 Farin/Stemmler: Mapping the CAF subtype-dependent reciprocal signaling in the CRC niche:
- P06 Günther/Naschberger: Impact of vascular plasticity on therapy responses in CRC:
- P08 Weigert: The role of IL-38 in shaping tumor-promoting versus protective inflammation in colorectal cancer:
- P09 Koop/Neurath: Unraveling the role of stromal IL-36R signaling in colorectal tumorigenesis:
- P15 Hildner: Tumor stroma-derived signals impair cDC1-dependent checkpoint inhibition as a potential resistance mechanism of colorectal cancer immunotherapy:
- P17 Ziegler: STAT3-controlled cross-dressing of dendritic cells in anti-tumor immunity:
- 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.
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-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