The PD-L1 protein, also known as programmed death-ligand 1 or CD274, is encoded by the CD274 gene. This gene is located on chromosome 9p24.1. PD-L1 has a molecular weight of approximately 40-50 kDa. Post-translational modifications of PD-L1 include glycosylation and phosphorylation, which can modulate its stability and function. PD-L1 is primarily a membrane protein, although it can also be found in the cytoplasm of cells.
PD-L1 is expressed in various tissues and cell types throughout the body, with particularly high levels observed in immune cells, such as antigen-presenting cells (APCs), T cells, and B cells. It is also expressed in non-immune cells, including epithelial cells, endothelial cells, and certain tumor cells. Various stimuli, including cytokines, growth factors, and inflammatory signals, can induce PD-L1 expression.
The function of PD-L1 is to regulate immune responses by interacting with its receptor, programmed cell death protein 1 (PD-1), expressed on the surface of activated T cells. The binding of PD-L1 to PD-1 inhibits T cell activation and effector functions, leading to T cell exhaustion and immune tolerance. This interaction is crucial in maintaining immune homeostasis and preventing excessive immune responses that could lead to tissue damage or autoimmunity.
Dysregulation of the PD-L1/PD-1 pathway has been implicated in various diseases and conditions, particularly cancer and autoimmune diseases. In cancer, tumor cells often upregulate PD-L1 expression as a mechanism to evade immune surveillance and suppress anti-tumor immune responses. Therefore, PD-L1 has emerged as a significant therapeutic target for cancer immunotherapy. Monoclonal antibodies targeting PD-L1 or PD-1, known as immune checkpoint inhibitors, have been developed to block the PD-L1/PD-1 interaction and unleash anti-tumor immune responses. These immunotherapy approaches have shown significant clinical efficacy and durable responses in various cancer types, including melanoma, lung cancer, and bladder cancer, highlighting the therapeutic potential of targeting PD-L1 in cancer treatment. Additionally, PD-L1-targeted immunotherapy has been explored in treating autoimmune diseases, such as rheumatoid arthritis and lupus, where blocking PD-L1 can restore immune tolerance and alleviate autoimmune symptoms.
Targeting PD-L1 with monoclonal antibodies (mAbs) has become a pivotal strategy in cancer immunotherapy. Several PD-L1 inhibitors have been developed and evaluated in clinical trials. Pembrolizumab (Keytruda), atezolizumab (Tecentriq), and durvalumab (Imfinzi) are examples of FDA-approved PD-L1 inhibitors. These mAbs work by blocking the interaction between PD-L1 on tumor cells and its receptor PD-1 [link] on immune cells, thereby restoring anti-tumor immune responses, and have demonstrated significant clinical benefits across various cancer types, including non-small cell lung cancer, melanoma, bladder cancer, and others.
Additionally, PD-L1 expression has been explored as a predictive biomarker for response to PD-L1 inhibitor therapy. Tumors with high PD-L1 expression have shown increased response rates to PD-L1 inhibitors. However, PD-L1 expression alone may not be sufficient to predict treatment response accurately, and its utility as a biomarker remains an area of active research.
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Synonyms
Programmed cell death 1 ligand 1, B7 homolog 1, B7 homolog 1; B7-H1; CD274; PD-L1; PDCD1 ligand 1; PDCD1L1; PDCD1LG1; Programmed cell death 1 ligand 1
Research Areas
Immuno Oncology, Immunology, Mast Cell Marker, PD-1 blockade immunotherapy, Signal Transduction