File:13046 2019 1094 Fig6 HTML.webp

English: Mechanisms of action of immune checkpoint inhibitors. Two signals are required to initiate the activation of T cells. The first signal involves the binding of a MHC to a TCR on T-cells. The second signal arises with the binding of the APC B7 ligands, CD80 or CD86, to CD28 on T-cells. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) competes with CD28 for the B7 ligands, which suppresses T-cell activity. Programmed cell-death protein 1 (PD-1) is also a negative regulator of T-cell activity that is able to bind to programmed cell-death 1 ligand 1 (PD-L1) on tumor cells, leading to T-cell ‘exhaustion’. Therefore, agents that act to block CTLA-4, PD-1 or PD-L1, are able to produce an anti-tumor response through immune activation. A number of these agents, including ipilimumab, tremelimumab, nivolumab, atezolizumab, durvalumab and avelumab, have been extensively studied in clinical trials for the treatment of cancer