Tumor stroma-derived signals impair cDC1-dependent checkpoint inhibition as a potential resistance mechanism of colorectal cancer immunotherapy
Project Leader
Research Focus
Surprisingly, the contribution of dendritic cell subsets to the CRC TME is only incompletely understood. To this end, P15 aims to analyze the function of conventional dendritic cell 1 (cDC1) subset of tissue-residing cDCs and test the hypothesis that these cells contribute significantly to the resistance to check point inhibition of microsatellite stable colorectal cancers. Specific focus will be placed on the identification of signaling networks that regulate cDC1 and that could be therapeutically targeted to enhance responsiveness to immunotherapy.
Main Collaborations
- P01 Greten: Modulating CAF plasticity to enable immunotherapy of colorectal cancer:
- P02 Büttner/Flinner: Multi modal prediction of therapy response for rectal cancer patients:
- P04 Farin/Stemmler: Mapping the CAF subtype-dependent reciprocal signaling in the CRC niche:
- P05 Neufert: The role of LIFR signaling in CAFs in CRC:
- P17 Ziegler: STAT3-controlled cross-dressing of dendritic cells in anti-tumor immunity:
- 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
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.
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