If the antigen continues to persist (e.g., as in case of chronic infection or tumor), continuously activated CD8+T lymphocytes progress toward an exhausted phenotype—charactarized by transcriptional and epigenetic changes, increased inhibitory receptors (IRs) expression, decreased functional molecules (e.g., perforin, granzyme, interferon-γ (INF-γ), and tumor necrosis factor-β (TNF-β)), and decreased cell proliferation capacity (interleukin-2 (IL-2) downregulation)—thus significantly reducing the killing effect on pathogens or tumors (12). This evidence concerns the gene CD8A and neoplasm.