Regulatory T Cells: A New Frontier in Cancer Immunotherapy

Tumor-specific immune-mediate cancer therapy was documented in a mouse model about one and half century ago (1). Nonetheless, the success of immune-based cancer treatments in humans has remained quite modest despite advances in our understanding and technology. The current paradigm driving most immune strategies is that tumors express tumor-associated antigens (TAA), thereby making them the objects of immune attack. These TAA should then be captured by professional antigen-presenting cells, particularly dendritic cells, which in turn prime naïve T cells to become TAA-specific effector cells through T cell cosignaling molecules and other mediators. This paradigm predicts that the solution to improving the efficacy of tumor immunotherapy is to augment TAA expression, boost cosignaling, or increase the number of effector T cells or professional antigen-presenting cells. Experience shows, however, that with a few limited exceptions, such strategies do not yield durable clinical successes.