CTLA4 and cancer: A similar process of constant antigenic stimulation of the TCR is thought to occur within the cancer TME and contribute to establishing a population of exhausted T-cells phenotypically identified by increased expression of inhibitory receptors such as PD-1 (programmed cell death-1), CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), TIM-3, LAG-3 (anti-lymphocyte activation gene-3), and VISTA (52, 61).