Figure 1.

Generation and recruitment of adaptive/induced Tregs in the tumor microenvironment. Tumor cells may secrete an array of cytokines and soluble factors that facilitate the induction of Foxp3 in Foxp3− cells or the recruitment of multiple cell types including natural Treg cells, myeloid-derived suppressor cells (MDSC), dendritic cells (DC), and macrophages. These cells in turn may secrete inhibitory and immune-suppressive factors such as TGF-β, IL-10, and indoleamine 2,3-dioxygenase (IDO) that could potentially convert some Foxp3− CD4+ cells into Foxp3+ cells. Additionally, tumor-derived factors or Treg interaction with DCs may promote generation of tolerogenic or immature DC (iDC) that recruit distinct populations of natural Tregs. nTreg is CD4+Foxp3+ cells while iTreg is CD4+Foxp3 variable.