The general notion is that the chronic stimulation by tumor antigens and the exposure of suppressive cytokines, drive TILs to differentiate into an exhausted phenotype characterized by the expression of immune checkpoint molecules such as programmed cell death-1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene- 3 (LAG-3), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and T-cell Ig and ITIM domain (TIGIT). The gene discussed is CTLA4; the disease is neoplasm.