This gene encodes an immune inhibitory receptor ligand that is expressed by hematopoietic and nonhematopoietic cells, such as T cells and B cells and various types of tumor cells. The encoded protein is a type I transmembrane protein that has immunoglobulin Vlike and Clike domains. Interaction of this ligand with its receptor inhibits Tcell activation and cytokine production. During infection or inflammation of normal tissue, this interaction is important for preventing autoimmunity by maintaining homeostasis of the immune response. In tumor microenvironments, this interaction provides an immune escape for tumor cells through cytotoxic Tcell inactivation. Expression of this gene in tumor cells is considered to be prognostic in many types of human malignancies, including colon cancer and renal cell carcinoma. Alternative splicing results in multiple transcript variants.
B7-H, B7H1, PDL1, PD-L1, PDCD1L1, PDCD1LG1
Plasma membrane, Endosome
Diseases associated with CD274 include Testicular Lymphoma and Smoldering Myeloma.
Involvement in Disease
Its related pathways are Innate Immune System and Class I MHC mediated antigen processing and presentation.
1.It plays a key role in inducing and maintaining immune tolerance to oneself (PubMed:11015443, PubMed:28813417, PubMed:28813410). As a ligand for the inhibitory receptor PDCD1/PD-1, it regulates the activation threshold of t cells and limits the effector response of t cells (PubMed:11015443, PubMed:28813417, PubMed:28813410). Through an unknown activation receptor, it is possible to stimulate a subset of T cells to mainly produce interleukin 10 (IL10) (PubMed: 10581077). 2. Tumors use the pdcd1 mediated inhibitory pathway to weaken anti-tumor immunity and escape the destruction of the immune system, thereby promoting tumor survival (PubMed:28813417, PubMed:28813410). The interaction with PDCD1/PD-1 inhibits the effector function of cytotoxic T lymphocytes (CTLs) (similar). The blockade of the pdcd1 mediated pathway leads to the reversal of the exhausted T cell phenotype and the normalization of the anti-tumor response, which provides a theoretical basis for cancer immunotherapy (through similarity).
Field of research
1.Ubiquitinated; STUB1 likely mediates polyubiquitination of PD-L1/CD274 triggering its degradation. 2.Glycosylation at Asn35, Asn192, Asn200, and Asn219 3.Modification sites at PhosphoSitePlus
Protein Based Therapies
Monoclonal antibody (mAb)
Atezolizumab (trade name Tecentriq) is a humanized monoclonal antibody that specifically targets cell death ligand 1 (PD-L1) programmed for proteins expressed on the surface of tumors. Atezolizumab was approved by the FDA on October 18, 2016 to prevent the interaction of PD-L1 and PD-1 and eliminate the inhibitory effect on the immune response seen in some cancers.
Lung Cancer Small Cell Lung Cancer (SCLC)
Metastatic Non-Small Cell Lung Cancer
Triple Negative Breast Cancer (TNBC)
Urothelial carcinoma ureter metastatic
Locally advanced Urothelial Carcinoma