Sarcoma Immunotherapy: Past Approaches and Future Directions

Figure 3

Mechanism of action of CTLA-4 and PDL1 blockade. (a) Activation of T cell requires interaction of MHC bearing tumor antigen with the TCR and interaction of the costimulatory molecule B7 with CD28. CTLA-4 is a negative regulator of the immune response that competes with CD28 binding with B7. Ipilimumab is a monoclonal antibody that binds CTLA-4 and promotes continued T cell activation. (b) The role of the PD-1 receptor is more significant in the peripheral tissue, once T cell activation has already occurred. After antigen exposure, PD-1 receptor is expressed on the T cells. When the PD-1 receptor interacts with its ligands PD-L1 and PD-L2, there is negative regulation of T cells in the tumor microenvironment. Blocking PD-1 or PD-L1 leads to activation of T cells. Reference: figure modified from [57].