Model of the accumulation of T_regcells in human tumors. One of the possible scenarios for how T_reg-cell attraction to the tumor site and expansion of T_reg cells occurs may be the release of CCL22 as well as H-ferritin by tumor cells and tumor-infiltrating macrophages leading to the accumulation of CCR4⁺ naive T_reg cells in the tumor microenvironment. Interaction with PGE₂-induced tolerogenic DCs then gives rise to the differentiation and peripheral expansion of naive T_reg cells into memory T_reg cells. Together with tolerogenic DCs, these T_reg cells than inhibit the generation of effector T cells, resulting in the induction of tolerance against the tumor.