Immunotherapy of Cancer by Targeting Regulatory T cells

• Regulatory T cells are involved in immunosuppressive tumor microenvironment. • Targeting Regulatory T cells represents a promising antitumor immunotherapy. • Immunotherapies by targeting Treg cells by using regulators are reviewed. • Include immune checkpoints, co-stimulatory molecules, cytokine receptors and agents. • Points to the future direction of this therapy. • Provides timely and comprehensive information on immunotherapies. Regulatory T (Treg) cells maintain immune homeostasis by inhibiting abnormal/overactive immune responses to both autogenic and nonautogenic antigens. Treg cells play an important role in immune tolerance, autoimmune diseases, infectious diseases, organ transplantation, and tumor diseases. Treg cells have two functional characteristics: T cell anergy and immunosuppression. Treg cells remain immune unresponsive to high concentrations of interleukin-2 and anti-CD3 monoclonal antibodies. In addition, the activation of Treg cells after TCR-mediated signal stimulation inhibits the activation and proliferation of effector T cells. In the process of tumor development, Treg cells accumulate locally in the tumor and lead to tumor escape by inducing anergy and immunosuppression. It is believed that targeted elimination of Treg cells can activate tumor-specific effector T cells and improve the efficiency of cancer immunotherapy. Therefore, inhibition/clearance of Treg cells is a promising strategy for enhancing antitumor immunity. Here, we review studies of cancer immunotherapies targeting Treg cells.