Programmed cell death protein 1 ligand 1 (PD-L1)

PD-L1, also known as Programmed death-ligand 1, is a key immune checkpoint molecule that plays a critical role in immune regulation and cancer immunotherapy. It is a 40kDa type 1 transmembrane protein belonging to the B7 family, encoded by the CD274 gene. PD-L1 is expressed on various cell types, including tumor cells, antigen-presenting cells, and other tissue cells. It functions by binding to its receptor, Programmed cell death protein 1 (PD-1), which is expressed on activated T cells, B cells, and macrophages. This interaction initiates an inhibitory signal that suppresses T cell activation and function, involving the inhibition of signaling pathways such as ZAP70 phosphorylation, PKC-θ activation, NF-κB, and AP-1. The PD-1/PD-L1 pathway normally helps maintain immune homeostasis and prevent autoimmunity by suppressing T cell responses. In cancer, tumor cells often overexpress PD-L1 as a mechanism to evade immune surveillance by suppressing tumor-reactive T cells. The understanding of this pathway has led to the development of immune checkpoint inhibitors that block the PD-1/PD-L1 interaction, thereby restoring anti-tumor immunity. PD-L1 expression on tumor cells is often used as a biomarker to predict response to anti-PD-1/PD-L1 therapy.

Other names

Programmed death-ligand 1CD274

Therapeutic drugs targeting PD-L1, primarily monoclonal antibodies, block the interaction between PD-L1 and its receptor PD-1, thereby preventing the inhibitory signal and reinvigorating anti-tumor immune responses.