Figure 5.

Mechanisms of immune exclusion in melanoma through WNT/β-catenin-signaling [172]. β-catenin induces expression of ATF3 and ATF3 represses transcription of CCL4. CD103⁺ dendritic cells and cytotoxic CD8⁺ T-cells are not recruited to melanoma, which leads to non-inflamed tumor. When β-catenin-signaling is inactive in melanoma cells, ATF3 is not expressed, which restores CCL4 production and secretion. This stimulates recruitment of immune cells, including CD103⁺ dendritic cells that activate CD8⁺ T cells. Recruitment of tumor specific CD8⁺ T cells in the tumor microenvironment results in immune inflamed melanoma. ATF3—activating transcription factor 3; β- cat—β- catenin; CCL4—CC-motif chemokine ligand 4.