Mechanism of antitumor immunity and immune checkpoint inhibitors. Tumor surveillance is mediated through a series of activating and inhibitory signals. T-cell activation occurs through signal 1 (between the TCR and the MHC complex) and signal 2 (between CD28 and the B7 receptor on APCs). The CTLA-4 receptor on T-cells competes with CD28 for B7 ligands to terminate T-cell activation in the priming phase. PD-1 is expressed on effector T-cells and binds to PD-L1 on tumor cells to exhaust T-cells and suppress its antitumor effect. Blockade of CTLA-4 (anti-CTLA-4), PD-1 (anti-PD-1) or PD-L1 (anti-PD-L1, not included in this figure) restores host immune function and induces antitumor activity. Reproduced with permission from Raman R and Vaena D. Biomed Res Int 2015; 2015:367354 [5], copyright ©2015. TCR, T-cell receptor; MHC, major histocompatibility complex; APCs, antigen-presenting cells; CTLA-4, cytotoxic T-lymphocyte antigen-4; PD-1, programmed death-1; PD-L1, programmed death-ligand 1. Figure from Immunotherapy in metastatic renal cell carcinoma: a comprehensive review[5].