IKK? Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells

Goektuna SI, Canli O, Bollrath J, Fingerle AA, Horst D, Diamanti MA, Pallangyo C, Bennecke M, Nebelsiek T, Mankan AK, Lang R, Artis D, Hu Y, Patzelt T, Ruland J, Kirchner T, Taketo MM, Chariot A, Arkan MC, Greten FR (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 7

Pages Range: 1914-25

Journal Issue: 6

DOI: 10.1016/j.celrep.2014.05.006

Abstract

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

Authors with CRIS profile

Roland Lang Professur für Angeborene Immunität und Pathogenerkennung

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) University of Liège (ULg) / Université de Liège BE Belgium (BE) Kyoto University / 京都大学 Kyōto daigaku JP Japan (JP) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) National Cancer Institute (NCI) US United States (USA) (US) University of Pennsylvania US United States (USA) (US)

How to cite

APA:

Goektuna, S.I., Canli, O., Bollrath, J., Fingerle, A.A., Horst, D., Diamanti, M.A.,... Greten, F.R. (2014). IKK? Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells. Cell Reports, 7(6), 1914-25. https://doi.org/10.1016/j.celrep.2014.05.006

MLA:

Goektuna, Serkan I., et al. "IKK? Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells." Cell Reports 7.6 (2014): 1914-25.

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