Background:

B7-H1, also called programmed death ligand (PD-L1) is a protein in the B7 family of immune proteins. PD-L1 binds to its receptor, PD-1, found on activated T cells, B cells, and myeloid cells, to modulate activation or inhibition. Engagement of PD-L1 with PD-1 on T cells delivers a signal that inhibits TCR-mediated activation of IL-2 production and T cell proliferation. The mechanism involves inhibition of ZAP-70 phosphorylation and its association with CD247 (1). PD-L1 signaling attenuates PKC-8 activation loop phosphorylation (resulting from TCR signaling), necessary for the activation of transcription factors NF-κB and AP-1 and for the production of IL-2. Upon IFN-γ stimulation, PD-L1 is expressed on T cells, NK cells, macrophages, myeloid DCs, B cells, epithelial cells, and vascular endothelial cells (2). Type I interferons can also upregulate PD-L1 on murine hepatocytes, monocytes, DCs, and tumor cells (3). It appears that upregulation of PD-L1 is a mechanism that cancers can employ to evade the host immune system as patients with higher expression levels of PD-L1 had a significantly poorer prognosis (4).