Figure 1. Model for MDSC recruitment in SmoM2-dependent tumors. Activation of hedgehog signaling in keratinocytes via expression of a constitutively activated, mutant smoothened (SmoM2) results in increased transforming growth factor β (TGFβ) signaling, primarily via TGFβ2. Activation of TGFβ signaling is observed in many cell types, including fibroblasts, CD11b⁺Gr1⁺ cells, and T cells. Since CD11b⁺Gr1⁺ cells are not present in skin tissues before tumor formation, secreted TGFβ2 presumably travels through the peripheral blood, possibly facilitated by tumor-derived exosomes. As a result of TGFβ signaling activation, the expression of chemokine (C-C) motif ligand 2 (CCL2) is increased in the tumor microenvironment (TME), whereas chemokine (C-C) motif receptor 2 (CCR2) expression is increased in myeloid derived suppressor cells (MDSC). Circulating MDSCs migrate toward the CCL2-enriched TME and remain to foster an immunosuppressive TME.