Fig. 2: Immune checkpoint modulation of the T cell activity

a APCs, loaded with antigenic peptides for presentation to the TCR by MHC, are unable to activate T cells in peripheral lymphoid organs through CD80/86:CD28 co-stimulatory signals. This inhibition is due to CTLA-4 sequestration of CD80/86 molecules (left). In tumor microenvironment, PD-L1/L2 expressed by melanoma cells link the co-inhibitory PD-1 molecule on activated T cells limiting their effects against tumor cells. This process can eventually lead to T cell exhaustion and immune escape of tumor cells (right). b T cell activation is obtained either in peripheral lymphoid organs (left) or in the tumor microenvironment (right) by anti-CTLA-4 or anti-PD-1 and anti-PD-L1 or -L2 antibodies, respectively. The abrogation of each immune checkpoint pathway by interruption of CTLA-4:CD80/86 or PD-1:PD-L1/L2 binding restores the immune response against melanoma cells