Tumor necrosis factor receptor superfamily member 1B (TNFR2) (TNFR2)

Tumor necrosis factor receptor superfamily member 1B (TNFR2) is a transmembrane receptor that mediates the pleiotropic effects of tumor necrosis factor (TNF), particularly the membrane-bound form (mTNF) (UniProt P20333). The TNF/TNFR2 ligand-binding interface is a critical structural domain where the trimeric TNF ligand interacts with the extracellular cysteine-rich domains of the receptor to initiate intracellular signaling (PubMed: 28133229). Unlike TNFR1, which is ubiquitously expressed and often associated with pro-inflammatory and apoptotic pathways, TNFR2 is primarily expressed on immune cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), where it promotes cell survival and immune suppression (PubMed: 30108713). In the context of oncology, the TNF/TNFR2 interface is considered a high-priority target because its activation helps tumors evade the immune system; thus, antagonistic antibodies are being developed to block this specific interaction (PubMed: 29345550). Conversely, in autoimmune and neurodegenerative diseases, agonists that stabilize or mimic the ligand-binding interface are being explored to enhance Treg activity and promote tissue regeneration (ClinicalTrials.gov: NCT04752826). Current therapeutic agents include broad TNF inhibitors like etanercept, which prevents TNF from binding to the interface, and newer, more selective monoclonal antibodies like BI-1808 that specifically target the receptor side of the interface (StatPearls: NBK534811).

Other names

TNFRIITumor necrosis factor receptor 2CD120bp75TNFRSF1BTNF-R2TBP-2

Antagonism of the TNF/TNFR2 ligand-binding interface to block immunosuppressive signaling in cancer or agonism of the interface to expand regulatory T cells in autoimmune disorders.