DcR3

Decoy receptor 3 (DcR3, TNFRSF6B) is a soluble member of the TNF receptor superfamily that lacks a transmembrane region and is secreted as a 35-kDa glycoprotein neutralizing three TNF-family ligands: Fas ligand (FasL), LIGHT and TL1A. By intercepting these ligands, DcR3 blocks Fas-mediated apoptosis, LIGHT-HVEM/TNFR1/2 and TL1A-DR3 signaling, thereby dampening apoptosis and inflammatory pathways. DcR3 is physiologically expressed in lung, colon, stomach, spleen and fetal tissues, and is strongly upregulated during inflammation and in numerous malignancies (gliomas, gastrointestinal, hepatobiliary, pulmonary and hematologic cancers), where tumor-derived DcR3 promotes immune evasion, resistance to apoptosis and angiogenesis. Beyond neutralization, DcR3 exerts ligand-independent actions: it induces dendritic-cell differentiation, skews macrophages toward an M2-like phenotype via heparan sulfate proteoglycan binding and can enhance monocyte adhesion. Elevated serum DcR3 serves as a biomarker of tumor burden and inflammatory disease severity, including inflammatory bowel disease and allergic inflammation.