This subset, mainly found in the peritumoral compartment in the tumor microenvironment, was characterized by an activated effector phenotype with elevated expression levels of PD-1, CTLA-4, Tim-3 and Lag-3 checkpoints, but, rather than exhausted, was shown upon ex- vivo polyclonal activation to express higher levels of Granzyme B and effector cytokines as compared to its CD8+FoxP3- counterparts. The gene discussed is CD8A; the disease is neoplasm.