The interplay of effector and regulatory T cells in cancer

Regulatory T (T_reg) cells suppress effector T (T_eff) cells and prevent immune-mediated rejection of cancer. Much less appreciated are mechanisms by which T_eff cells antagonize T_reg cells. Herein, we consider how complex reciprocal interactions between T_eff and T_reg cells shape their population dynamics within tumors. Under states of tolerance, including during tumor escape, suppressed T_eff cells support T_reg cell populations through antigen-dependent provision of interleukin (IL)-2. During immune activation, T_eff cells can lose this supportive capacity and directly antagonize T_reg cell populations to neutralize their immunosuppressive function. While this latter state is rarely achieved spontaneously within tumors, we propose that therapeutic induction of immune activation has the potential to stably disrupt immunosuppressive population states resulting in durable cancer regression.