The mitochondrial complex III appears to be required for the inhibition of Tregs function.339 Kunisada and colleagues also found that metformin reduced the amount of tumor-infiltrating Tregs by suppressing the differentiation of naive CD4+ T cells.340 The MDSCs induced by tumors also inhibited T cells proliferation and increased colorectal carcinoma cell growth by producing ROS341 while the negative effect of MDSCs can be suppressed by catalase, thus restoring T cells action.342 ROS are also involved in the activation of macrophage signaling. Here, CD4 is linked to neoplasm.