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

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