IKK? 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?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.     «

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 o...     »