PD-1/PD-L1 CHECKPOINT

PD-1 represents another important immune checkpoint receptor. The major role of PD-1 is to limit the activity of T cells in the peripheral tissues at the time of an inflammatory response to infection and to limit autoimmunity. This is, therefore, a major immune resistance mechanism within the tumor microenvironment.

PD-1 expression is induced when T cells become activated. PD-1 inhibits signaling molecules involved in T-cell activation when engaged by one of its ligands, either PD-L1 or PD-L2, downregulating T-cell activity. In healthy tissue, PD-L1 is expressed to prevent T-cell attack.

PD-1 is expressed more broadly than CTLA-4. For example, it is expressed on other activated non-T-cell subsets, including B cells and natural killer cells, where it limits the cell-killing activity of these cells. Importantly, PD-1 is expressed on a large proportion of CD4+ tumor-infiltrating lymphocytes from many different tumor types. To suppress the cytotoxic activity of these cells, many different human tumors have been found to express the PD-L1 and PD-L2 ligands.

The major PD-1 ligand to be expressed on solid tumors is PD-L1. This inhibits local antitumor T-cell responses, and serves as a mechanism by which tumors may evade the body's immune response as shown in the video below.

Binding of PD-L1 and PD-L2 with their receptors results in T-cell deactivation.

Blocking the PD-1 pathway holds the potential to enhance antitumor T-cell function in the tumor microenvironment. For more information, select the button to view animation.

Select the video icon below to learn more about PD-L1 Checkpoint in the immune response.