CD274/PD-L1/B7-H1
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Introduction to CD274/PD-L1/B7-H1
Drug targets a biomolecule that can directly bind to drugs and then react. Generally, the target refers to a protein, which is related to the cause of disease. The focus of the target began with focusing on tumors and then began to spread to various fields. Introduction to CD274/PD-L1/B7-H1 protein is a common target in medicine.
B7-H1, referred to as Programmed cell death 1 ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7-H1, is encoded by the CD274 gene. PD-L1 is a ligand for PD-1, that is, a protein that can bind to PD-1. It consists of 290 amino acid residues, including mainly the short cytoplasmic tail region, the transmembrane region, and the IgV and IgC-like extracellular domains. PD-L1 is expressed in both hematopoietic and nonhematopoietic cells and on the tumor surface. PD-L1 is also expressed on the surface of antigen-presenting cells (DC cells, macrophages, etc.), and the surface of vascular endothelial cells.
Function of Target CD274/PD-L1/B7-H1
By binding to PD-1, PD-L1 conducts inhibitory signals, preventing T lymphocytes from effectively recognizing and attacking tumor cells, thus allowing tumor cells to escape the attack of the body's immune system.
Under normal physiological conditions, the interaction of PD-L1 with PD-1 helps to maintain the balance of the immune system and prevent autoimmune diseases caused by hyperactivation. And have demonstrated a role in the regulation of the immune response and peripheral tolerance. Play a key role in inducing and maintaining tolerance to autoimmunity. The blockade of the PDCD 1-mediated pathway can enable the reversal of the senescent T cell phenotype and normalize the anti-tumor response, providing a theoretical basis for cancer immunotherapy.
Gene Pathway of Target CD274/PD-L1/B7-H1
IRF-1 promotes PD-L1 expression, while phosphorylated STAT 1-induced transcription of the interferon-stimulated gene (ISG) enhances the immune response and suppresses T cell activation, proliferation, and cytokine secretion. Activation of PD-1 / PD-L1 signaling pathway can also induce apoptosis of T cells, further weakening the body's anti-tumor immune response. Under physiological conditions, the activation of the PD-L1 signaling pathway helps to maintain immune tolerance and prevent the development of autoimmune diseases. By inhibiting T cell hyperactivation, the PD-L1 signaling pathway can protect normal tissue from immune damage.
Fig 1: PD-L1 Gene Pathway (Reference documentation: Gou Q, Dong C, Xu H, Khan B, Jin J, Liu Q, Shi J, Hou Y. PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis. 2020 Nov 6;11(11):955.)
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Reference
[1] Fabrizio FP, Trombetta D, Rossi A, Sparaneo A, Castellana S, Muscarella LA. Gene code CD274/PD-L1: from molecular basis toward cancer immunotherapy. Ther Adv Med Oncol. 2018 Dec 17;10:1758835918815598.
[2] Tang N, Yang Y, Xie Y, Yang G, Wang Q, Li C, Liu Z, Huang JA. CD274 (PD-L1) negatively regulates M1 macrophage polarization in ALI/ARDS. Front Immunol. 2024 Feb 19;15:1344805.
[3] Gou Q, Dong C, Xu H, Khan B, Jin J, Liu Q, Shi J, Hou Y. PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis. 2020 Nov 6;11(11):955.
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2018-07-16
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