SMAD3 and neoplasm: Furthermore, tumor or immune-cell-derived regulating factors, including FoxP3 (forkhead box protein P3), CCL22/CCR4, OX40L/OX40 (tumor necrosis factor superfamily member 4/tumor necrosis factor receptor superfamily member 4), and SMAD3 (SMAD family member 3) also determine the maintenance of the immunosuppressive CC TIME (Figure 3) [108].