Role of CD4⁺CD25⁺FOXP3⁺ T_Reg cells on tumor immunity

Not all T cells are effector cells of the anti-tumor immune system. One of the subpopulations of CD4⁺ T cells that express CD25⁺ and the transcription factor FOXP3, known as Regulator T cells (T_Reg), plays an essential role in maintaining tolerance and immune homeostasis preventing autoimmune diseases, minimalize chronic inflammatory diseases by enlisting various immunoregulatory mechanisms. The balance between effector T cells (T_eff) and regulator T cells is crucial in determining the outcome of an immune response. Regarding tumors, activation or expansion of T_Reg cells reduces anti-tumor immunity. T_Reg cells inhibit the activation of CD4⁺ and CD8⁺ T cells and suppress anti-tumor activity in the tumor microenvironment. In addition, T_Reg cells also promote tumor angiogenesis both directly and indirectly to ensure oxygen and nutrient transport to the tumor. There is accumulating evidence showing a positive result that removing or suppressing T_Reg cells increases anti-tumor immune response. However, depletion of T_Reg cells will cause autoimmunity. One strategy to improve or restore tumor immunity is targeted therapy on the dominant effector T_Reg cells in tumor tissue. Various molecules such as CTLA-4, CD4, CD25, GITR, PD-1, OX40, ICOS are in clinical trials to assess their role in attenuating T_Reg cells' function.