The role of IL-38 in shaping tumor-promoting versus protective inflammation in colorectal cancer
Project Leader
Research Focus
© A. Weigert
IL-38 is a member of the IL-1 family that confers important functions in the resolution of inflammatory processes. P08 will evaluate the notion that targeting IL-38 could be a valuable approach to enhance anti-tumor immunity in CRC potentially also sensitizing for immunotherapy. While various cell types in the colorectal TME upregulate IL-38 expression, their exact contribution and the respective downstream signaling events in IL-38 responsive cells are only partially understood. To identify the relevant target cells, cytotoxic lymphocytes will be analyzed by Phenoptics multispectral imaging and multicolor flow cytometry.
Main Collaborations
- P01 Greten: Modulating CAF plasticity to enable immunotherapy of colorectal cancer:
- P05 Neufert: The role of LIFR signaling in CAFs in CRC:
- P07 Berlin/Groß: Specific role(s) of the inflammasome in the TME of primary and metastasized sporadic CRC:
- P09 Koop/Neurath: Unraveling the role of stromal IL-36R signaling in colorectal tumorigenesis:
- P14 Kesselring/Minguet: The role of γδ T cells in the tumor microenvironment of colorectal cancer:
- P16 Fichtner-Feigl/Imkeller: The role of primary-CRC-derived adaptive immune cells in anti-metastasis 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
Inflammatory fibroblasts mediate resistance to neoadjuvant therapy in rectal cancer
Nicolas AM, Pesic M, Engel E, Ziegler PK, Diefenhardt M, Kennel KB, Buettner F, Conche C, Petrocelli V, Elwakeel E, Weigert A, Zinoveva A, Fleischmann M, Häupl B, Karakütük C, Bohnenberger H, Mosa MH, Kaderali L, Gaedcke J, Ghadimi M, Rödel F, Arkan MC, Oellerich T, Rödel C, Fokas E, Greten FR.
Cancer Cell. 2022 Feb 14;40(2):168-184.e13. doi: 10.1016/j.ccell.2022.01.004. Epub 2022 Feb 3. PMID: 35120600