Figure 3 – Schematic overview of PD-1 function and T cell mediated tumor cell death.

Activated T cells produce cytokines, including interleukin-2 (IL-2) which via autocrine and paracrine signaling lead to T cell proliferation. Activated T cells are capable of inducing T cell apoptosis via the Fas-Fas Ligand (FasL) system. Fas-FasL binding results in localized secretion of granzyme and perforin. This locally released complex is capable of inducing tumor cell apoptosis. PD-1 is also upregulated on the surface of activated T cells. PD-L1 is expressed on the surface of tumor cells, and when engaged with its receptor on the surface of T cells, PD-1, results in decreased T cell cytokine secretion, decreased activated T cell proliferation, and impaired T cell cytolytic function. Modulating PD-1 or PD-L1 with therapeutic antibodies can lead to effective anti-tumor immune responses. Please see accompanying text for further details.