When persistently exposed to tumor antigens, upregulation of inhibitory receptors such as PD-1, cytotoxic T lymphocyte associated antigen-4 (CTLA-4), TIGIT, T cell immunoglobulin-and mucin-domain-containing molecule-3 (TIM3), and lymphocyte activation gene-3 (LAG3) can lead to impaired killing function and exhaustion of CD8+ T cells (43, 44). The gene discussed is HAVCR2; the disease is neoplasm.