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Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), also known as Decoy receptor 3 (DcR3), is a soluble secreted protein that lacks a transmembrane domain [1, 2]. It acts as a decoy by binding and neutralizing three ligands of the TNF superfamily: Fas ligand (FasL), LIGHT (TNFSF14), and TL1A (TNFSF15) [3, 13]. By competing with functional receptors for these ligands, DcR3 inhibits apoptosis, suppresses T cell activation, and modulates the immune response [3, 5]. It is frequently overexpressed in various cancers, such as gastrointestinal and pancreatic tumors, where it facilitates immune evasion and tumor cell survival [5, 13, 23]. In inflammatory and autoimmune diseases like sepsis and rheumatoid arthritis, DcR3 levels correlate with disease severity and serve as a prognostic biomarker [1, 4, 8]. Therapeutic approaches involve using recombinant DcR3-Fc fusion proteins to dampen excessive inflammation or developing inhibitors to block its pro-tumorigenic effects [5, 9, 24].
Competitive neutralization of FasL, LIGHT, and TL1A ligands; modulation of macrophage and dendritic cell differentiation via heparan sulfate proteoglycan binding.
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