Figure 2.

Schematic diagram of immune checkpoint blockade. MHC generally presents antigen on the surface of cancer cells for recognition by CD8⁺ T cells via their TCR. CTLA4, as a negative regulator, is homologous to the T cell co-stimulatory protein CD28, both of which bind to CD80 and CD86 on the surface of cancer cell but with different affinity. Overall, CTLA4 has a much higher affinity than CD28 to CD80/CD86. PD1 is expressed on T lymphocyte surface. The binding of PD1 on the T cell with PDL1 functions to suppress signals downstream of TCR activation, leading to apoptosis of the CTL. Antibodies (anti-CTLA4, anti-PD1, anti-PDL1) inhibit these checkpoint targeting proteins to restore the activity of T cells and kill cancer cells. MHC, major histocompatibility complex; TCR, T cell receptor; Ag, antigen.