PD-L1 (CD274)
PD-L1 (programmed death-ligand 1) is the cell-surface ligand that engages PD-1 on T cells and transmits the “stand down” signal tumors use to disable immune attack.
Function
PD-L1 is expressed on antigen-presenting cells and on cells in immune-privileged sites, where its engagement of PD-1 limits T-cell activity. Its expression is inducible by inflammatory signals (interferon-γ) and by oncogenic pathways (PI3K, MYC), and in tumors it appears both on tumor cells themselves and on myeloid cells in the microenvironment. The ligand’s cytoplasmic tail has reported signaling roles of its own, so the PD-L1 interaction is bidirectional rather than a one-way brake.
In cancer
PD-L1 expression is the tumor’s principal immune-evasion display: it converts a site of active immune recognition into a site of T-cell exhaustion, and it is one of the escape phenotypes of immunoediting. PD-L1 immunohistochemistry is the companion diagnostic for PD-1/PD-L1 blockade, with the caveat that expression is heterogeneous and inducible — a negative stain does not guarantee a non-responsive tumor. Amplification of the CD274 locus occurs in Hodgkin lymphoma and other PD-L1-high tumors.
Notes
- Human gene symbol: CD274; UniProt Q9NZQ7; 238 amino acids; B7 immunoglobulin superfamily; IgV and IgC domains plus short cytoplasmic tail.