CD8+ T cell exhaustion or dysfunction is frequently observed in chronic viral infections and cancer due to persistent antigen exposure and chronic T cell receptor (TCR) signaling. The exhausted T cell state is associated with a decrease in proliferative capacity, reduced effector functions, changes in gene expression and metabolism, and elevated and sustained expression of multiple inhibitory receptors, including PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, and 2B4/CD244. Under steady state conditions, these...