CD4 + CD25 + regulatory T cells in tumor immunity

• Foxp3 is a critical regulator of CD4 + CD25 + regulatory T cell development and function.
• Possible mechanisms for Treg-mediated suppression
• The mechanism for Treg inhibition of tumor immune

Regulatory T cells (Tregs) are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. Depletion of Tregs results in the onset of a variety of autoimmune diseases. Tregs are defined based on expression of CD4, CD25, and the transcription factor, FoxP3. It is now clear that three inhibitory cytokines, IL-10, IL-35 and TGF-β, are key mediators of Tregs function. Tregs have been shown to be important contributors to the development of immune tolerance toward tumors and play a critical role in the induction of tolerance to tumor associated antigens and suppression of anti-tumor immunity. Increasing researches support the existence of elevated numbers of regulatory T cells in cancer patients. Poor prognosis and decreased survival rates are closely correlated with higher Treg cell frequencies. Depletion of Tregs or blockade of their immune inhibitory role can enhance anti-tumor effects. Recent evidence suggests that Tregs may be responsible for the failure of host anti-tumor immunity by suppressing cytotoxic T-cells. In this review, we discuss cellular and molecular mechanisms in the differentiation and function of Tregs in tumor immunity.