Figure 1.

Reprogramming of TIL Tregs to control tumor by targeting their stability. Left, Stable Treg. Treg and T_FR cells mainly suppress the cellular and humoral anti-tumor immune responses, respectively. Conversely, tumor cells impose suppression on both cellular and humoral immune responses, but foster the immune suppression by Treg and T_FR cells. Right, Unstable Treg. Factors or approaches destabilize or reprogram Treg and T_FR cells into effector-like cells, which display impaired suppressive activity, but instead cooperate with both cellular and humoral anti-tumor components to control tumor growth and progression. The peripheral events are not depicted, but strategies used to selectively reprogram TIL Tregs, but not Tregs in the periphery, are expected to be most effective without systemic adverse effects. The unclear events are indicated by dashed lines. Not depicted: Peripheral T_FH and B-cells and their migration into the tumor; expansion of Treg/T_FR cells and anti-tumor effector cells; other cells regulating anti-tumor responses (e.g., myeloid-derived suppressor cells and macrophages, etc.).