CTLA4 and melanoma: The persistent antigen exposure by melanoma cells is dependent on the up-regulation of immune checkpoints, such as programmed cell death 1 (PD1), cytotoxic T lymphocyte antigen 4 (CTLA4), T-cell immunoglobulin, and mucin-domain containing-3 (TIM3) or lymphocyte-activation gene 3 (LAG3) and results in negative feedback for the cytotoxic T-cells.