However, recent studies have demonstrated that continued exposure to tumor antigens and immunosuppressive tumor environments can induce both T and NK cell exhaustion (Roe, 2022, Jia et al., 2023), which further increases the expression of immune checkpoints including programmed death-1(PD-1), cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), and NK cell receptor 2 A (NKG2A) to reinforce exhaustion of cytotoxic T and NK cells (van Montfoort et al., 2018, Ducoin et al., 2022). The gene discussed is CTLA4; the disease is neoplasm.