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Figure 1. (A) Mechanism of action for ipilimumab and tremelimumab. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activity. T-cell activation requires two separate stimulatory signals. The first signal occurs when the TCR binds to the major histocompatibility complex (MHC) of an antigen-presenting cell (APC). The second signal, or co-stimulatory signal, occurs when the CD28 receptor of T cells binds the B7 ligand of APCs. CTLA-4 is a naturally occurring T-cell receptor that, when bound by B7 on APCs, prevents the co-stimulation required for T-cell activation and suppresses T-cell activity. Ipilimumab and tremelimumab are monoclonal antibody designed to bind CTLA-4 and prevent its binding of B7, allowing for T-cell activation and potentiation to occur, allowing for enhanced immune-mediated cytotoxicity. (B) Mechanism of action for immune checkpoint inhibitors: The binding of PDL-1 on tumor cells to PD-1 on T-cells prevents T cells from killing tumor cells. Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor allows cytotoxic activity of T cells against tumor cells. TCR: T cell receptor; PD: programmed cell death; L: ligand