TY  - JOUR
A1  - Göktuna, Serkan I.
A1  - Canli, Ozge
A1  - Bollrath, Julia
A1  - Fingerle, Alexander André
A1  - Horst, David
A1  - Diamanti, Michaela A.
A1  - Pallangyo, Charles
A1  - Bennecke, Moritz
A1  - Nebelsiek, Tim
A1  - Mankan, Arun K.
A1  - Lang, Roland
A1  - Artis, David
A1  - Hu, Yinling
A1  - Patzelt, Thomas
A1  - Ruland, Jürgen
A1  - Kirchner, Thomas
A1  - Taketo, Makoto Mark
A1  - Chariot, Alain
A1  - Arkan, Melek C.
A1  - Greten, Florian
T1  - IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells
T2  - Cell reports
N2  - The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ)-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC) therapy.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37245
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-372455
SN  - 2211-1247
N1  - This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
VL  - 7
IS  - 6
SP  - 1914
EP  - 1925
PB  - Cell Press
CY  - Maryland Heights, MO
ER  -