Mechanism of Action and Pharmacologic Features of Drugs Targeting PD ‐1/ PDL ‐1 and CTLA ‐4

The discovery of immune checkpoint proteins such as PD-1/PD-L1 and CTLA-4 triggered a revolution in the field of cancer immunotherapy, with antibodies (Abs) blocking these molecules being now part of the standard of care for several tumor types and the goal of immune checkpoint blockade (ICB) therapy is to remove molecular "brakes" suppressing the immune response against tumor cells. There are two major mechanisms of action behind Ab-based ICB therapy; direct blockade of the immune checkpoint molecule and depleting the effects of cells expressing high levels of immune checkpoint proteins. As the activity of PD-1 and PD-L1 inhibitors relies on the immune inhibitory interactions between tumor and immune cells through this pathway, these targets and the immune cells expressing them should be present in the TME for the drugs to work effectively.