Immune-therapeutics directed against negative immune regulatory pathways (checkpoint inhibitors) have been one of the biggest breakthroughs in cancer therapy of the recent years emphasizing the growing importance of tumor immunology. To further strengthen this research within the IAI we established this area. We determine the functions of Stat1, Stat3, and the Janus kinase family member TYK2 in the tumor microenvironment of colorectal cancer using conditional knock-out mice in combination with genetic and chemical intestinal tumor models. In addition we will analyze the mechanisms that modulate the transition from non-tumorigenic EGFR- macrophages to pro-tumorigenic EGFR+ macrophages and understand the role of EGFR in regulating the communication between tumor cells and other cells of the immune system. These studies will give insights into how the functional interaction between tumor cells and immune cells in different environmental niches is organized by EGFR. The results may have important consequences how inhibition of EGFR might be used in anti-tumor therapy in the future by specifically targeting distinct cell types, while excluding others.