In both cancer patients and preclinical models, intratumoral CD8 T cells that express activation markers including inhibitory receptors such as PD-1, LAG-3, and TIM-3 often exist in a terminally differentiated state and may display a range of functional capabilities from short-lived cytotoxic and cytokine producing CD8 T effector cells to dysfunctional or exhausted CD8 T cells that exist in a state of limited or restrained functional capabilities25. The gene discussed is CD8A; the disease is cancer.