Chronic inflammation can be a causative agent for several types of cancer, whereby inflammatory cells drive the initial steps of cancer formation and contribute to the progression of the disease. Hence, many immune cells infiltrate tumors, but their exact roles in the tumor microenvironment are not always clear. In this respect, a class of immune cells called mononuclear phagocytes, which include macrophages and dendritic cells, are important regulators of tumor growth and it has been suggested that manipulating these tumorassociated cells could be a new frontier in cancer therapy. This issue is very relevant for hepatocellular carcinoma (HCC), the most common type of liver cancer, since the liver contains a large pool of macrophages (Kupffer cells, KCs) and dendritic cells. However, thus far very little is known about the heterogeneity and the dynamics of liver mononuclear phagocytes, especially during HCC development and progression. Such knowledge is crucial if we aim to use these cells as therapeutic targets. In this project, we will employ novel transgenic mouse strains, in which KCs and DCs (or KCand DC-associated genes) can be specifically visualized and depleted, to study the dynamics and molecular and functional characteristics of these cells during distinct stages of HCC development in three independent mouse models. These data will provide an insight in the importance of these cells for HCC outcome.