Immune Chaperone gp96 Drives the Contributions of Macrophages to Inflammatory Colon Tumorigenesis

摘要: Macrophages are important drivers in the development of inflammation-associated colon cancers, but mechanistic underpinnings for their contributions not fully understood. Furthermore, Toll-like receptors have been implicated cancer, relevant cellular sites action obscure. In this study, we show that endoplasmic reticulum chaperone gp96 is essential tumor-associated macrophages (TAM) to license inflammatory tumorigenesis. Mice where was genetically deleted a macrophage-specific manner exhibited reduced colitis and Attenuation cancer these mice correlated strikingly with mutation rates β-catenin, increased efficiency DNA repair machinery, expression proinflammatory cytokines, including interleukin (IL)-17 IL-23 tumor microenvironment. The genotoxic nature TAM-associated inflammation evident by genes pathway. Our work deepens understanding how TAM promote oncogenesis altering molecular oncogenic program within epithelial cells, it identifies as lynchpin needed function impact on critical cytokines