Tumor necrosis factor receptor superfamily member 4 and Tumor necrosis factor ligand superfamily member 4 signaling axis (OX40/OX40L)

The OX40/OX40L signaling axis is a potent costimulatory pathway within the tumor necrosis factor (TNF) superfamily that plays a pivotal role in modulating T-cell-mediated immune responses. OX40 (CD134) is a receptor primarily expressed on activated CD4+ and CD8+ T cells, while its cognate ligand, OX40L (CD252), is typically expressed on antigen-presenting cells such as dendritic cells, B cells, and macrophages (UniProt P43489, P23510). Engagement of this axis promotes the survival and expansion of effector T cells and the development of immunological memory, while simultaneously antagonizing the suppressive activity of regulatory T cells (PubMed 25617462). In the context of oncology, therapeutic agonists are designed to stimulate this pathway to enhance the immune system's ability to recognize and destroy cancer cells (PubMed 20844024). Conversely, in inflammatory and autoimmune conditions like atopic dermatitis, monoclonal antibodies are utilized to block the OX40/OX40L interaction, thereby reducing the pathological T-cell activation that drives chronic inflammation (PubMed 33493432).

Other names

CD134/CD252 axisTNFRSF4/TNFSF4 signaling pathwayACT35TXGP1LGP34OX40 receptor and OX40 ligand

Agonism of OX40 enhances T-cell effector function and survival while inhibiting regulatory T-cell suppression to boost anti-tumor immunity; Antagonism or blockade of the OX40/OX40L interaction inhibits T-cell activation and pro-inflammatory cytokine release to treat autoimmune and inflammatory diseases.