IKKalpha promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells.

[en] 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 IkappaB kinase alpha (IKKalpha) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKalpha kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon gamma (IFNgamma)-expressing M1-like myeloid cells. In IKKalpha mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKalpha 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 IKKalpha as a promising target for colorectal cancer (CRC) therapy.

Research Center/Unit :

Giga-Signal Transduction - ULiège

Disciplines :

Oncology

Author, co-author :

Göktuna, Serkan ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Canli, Ozge

Bollrath, Julia

Fingerle, Alexander A.

Horst, David

Diamanti, Michaela A.

Pallangyo, Charles

Bennecke, Moritz

Nebelsiek, Tim

Mankan, Arun K.

More authors (10 more)

Language :

English

Title :

IKKalpha promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells.

Publication date :

2014

Journal title :

Cell Reports

eISSN :

2211-1247

Publisher :

Elsevier, Amsterdam, Netherlands

Volume :

Issue :

Pages :

1914-25

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

WELBIO - Walloon Excellence in Life Sciences and Biotechnology
F.R.S.-FNRS - Fonds de la Recherche Scientifique
Télévie
Fondation contre le Cancer

Commentary :

Available on ORBi :

since 03 March 2015

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