CXCR3-expressing macrophages regulate angiogenesis, tumor cell proliferation and immune evasion in hepatocellular carcinoma

Chemokine receptor CXCR3 shapes the intrahepatic tumor microenvironment in a highly dynamic manner. Genetic deletion of Cxcr3 has an impact on the development and differentiation of myeloid cells and improves potentially oncogenic properties of tumor-associated macrophages in hepatocellular carcinoma (HCC) bearing mice. This ultimately leads to an increased carcinogenesis. C57BL/6J wild type (WT) and Cxcr3 knockout mice (Cxcr3-/-) were treated with a combination of diethylnitrosamine (DEN) and tetrachloromethane (CCl4) to induce fibrosis-associated HCCs. For functional analysis of CXCR3 during macrophage differentiation a comprehensive in vitro and in vivo analysis was performed. For ATACseq in vitro cultured wild type and Cxcr3-/- common myeloid progenitor cells (CMP)/ granulocyte-monocyte progenitor (GMP) cells and moncytes were used.