(A) Activating signals to T cells, through anabolic metabolism induction (“feast”), drive cell division and functional differentiation (change from red to blue). Inhibitory signals oppose anabolic induction (“famine”) and functional maturation, thereby maintaining self-renewal (red). One cell can yield opposing outcomes in its daughter cells by unequal transmission of activating and inhibitory signals during cell division (color gradient in oval mitotic cell). (B) Activation, division, and differentiation (blue wedge) embody response intensity and narrowing of potential (loss of self-renewal). Self-renewing cells (red wedge) reiteratively remake themselves as they yield differentiated descendants, embodying response durability and multipotency. In the lower plot, inverse relationship between response intensity and durability is a potential vulnerability of cancer immunotherapies that focus on intensifying T cell responses in the setting of imperiled T cell durability. (C) List of mechanistic details in the duality of signaling, cell fate, metabolism, cell biology, and response dynamics. Improving immunotherapy may require creative strategies to contort the natural regenerative balance in order to optimize intensity along with greater durability.