However, upon continuous antigen exposure in chronic infections and cancer, effector T cells gradually become functionally exhausted, characterized by reduced cytokine production (IL-2, IFN-γ, and TNF-α), upregulated inhibitory receptors (programmed cell death 1 [PD-1], T cell immunoglobulin mucin receptor 3 [TIM-3], and lymphocyte activation gene 3 [LAG-3]), and alterations in their transcriptional and epigenetic profiles (20, 21, 23). Here, PDCD1 is linked to cancer.