An additional mechanism that hampers immune surveillance in the tumor microenvironment is the expression on tumor-infiltrating cytotoxic cells of several checkpoint inhibitory receptors including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death receptor-1 (PD-1), T cell-immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), lymphocyte activation gene 3 (LAG-3), TIGIT, and CD96, which are all responsible for the acquisition of a dysfunctional phenotype [68,69]. The gene discussed is HAVCR2; the disease is neoplasm.