Neutralizing Regulatory T Cells

The maintenance of peripheral tolerance against self and environmental antigens needs regulatory T cells (Treg) that deploy a variety of suppressive mechanisms to control potentially harmful inflammatory and autoimmune reactions. These mechanisms include production of suppressive cytokines and small molecules, expression of inhibitory receptors as well as direct cytolysis and intracellular transfer of second messengers. However, the tumors may hijack Treg immunosuppressive function to escape the anti-cancer immune responses. Expression of self- or altered-self antigens on tumor cells may drive Treg expansion and enhance their suppressive activity. Therefore, Treg-mediated immunosuppression represents one of the main hurdles to the anti-tumor immunity accounting for the failure of anti-tumor therapies including the vaccination and adoptive cell transfer. It has been shown that inhibition of Treg development, survival, and function can alleviate tumor-induced immunosuppression and improve the efficacy of anticancer immunotherapy. Here we discuss current strategies of targeting Treg development and function, including Treg depletion, inhibition of extracellular adenosine production and modulation of signaling pathways in Treg through cell surface receptors.

Keywords: CD25, CD73, costimulatory molecules, CTLA-4, FoxP3, GITR, IL-2, immunotoxins, OX40, regulatory T cells, suppression, vaccination.