Figure 1a.

Diagram of immune checkpoint inhibitor therapy shows immune inhibition by tumors and its blockade as the mechanism of action. MHC = major histocompatibility complex, TCR = T-cell receptor. (a) CTLA-4 is an immune checkpoint molecule on T cells, and its interaction with the ligand B7 on antigen-presenting cells causes inhibition of the T-cell immune response against the tumor, which allows the tumor cells to evade immune attack. CTLA-4 inhibitors such as ipilimumab prevent this interaction by binding to CTLA-4 on T cells and blocking T-cell immune inhibition, thereby activating an immune response against tumor cells. (b) The binding of PD-1 on effector T cells and of its ligand PD-L1 on tumor cells delivers an inhibitory signal that decreases cytokine production and T-cell proliferation, which allows tumor cells to escape from immune response. PD-1 or PD-L1 inhibitors block the binding and prevent tumoral immune inhibition, thus inducing an antitumor immune response. PD-1/PD-L1 blockade by agents such as nivolumab, pembrolizumab, atezolizumab, and durvalumab has become a major treatment option for many types of advanced cancers. (Adapted and reprinted under a CC BY 4.0 license from reference 8.)