Tumor necrosis factor superfamily member 4 (OX40 ligand) (OX40L)

OX40 ligand (OX40L, CD252, TNFSF4) is a type II membrane-bound glycoprotein belonging to the tumor necrosis factor superfamily that serves as a critical costimulatory ligand for the OX40 receptor on activated T cells.[1][3][7] OX40L is constitutively expressed on antigen-presenting cells including dendritic cells, macrophages, and activated B lymphocytes, and functions as a secondary costimulatory signal that enhances T cell activation, survival, proliferation, and memory formation following antigen recognition.[3][7][11] The OX40-OX40L interaction operates as an important immune checkpoint, promoting both Th1 and Th2-mediated immune responses and suppressing regulatory T cell function, making it a dual-use therapeutic target.[7][11] In cancer immunotherapy, agonistic approaches that enhance OX40L-OX40 signaling show promise for amplifying anti-tumor T cell responses,[7][11] while in autoimmune and inflammatory diseases, blocking this interaction has demonstrated efficacy in preclinical models for preventing pathogenic T cell responses.[1][11] The functional form of OX40L is a membrane-bound homotrimer assembled through its TNF homology domain, and engineering the oligomeric architecture of OX40L fusion proteins has proven critical for optimizing its agonistic therapeutic potential.[4][6]

Other names

gp34 (glycoprotein Gp34)TXGP-1CD252TNFSF4

Agonistic approaches (T cell activation): OX40L binds OX40 receptors on activated T cells, promoting OX40 trimerization. Trimerization recruits TRAF2, 3, and 5 adaptor proteins and activates NF-κB signaling pathway. Enhanced T cell survival, proliferation, cytokine production, and memory formation. Antagonistic approaches (autoimmune/inflammatory suppression): Blocking OX40-OX40L interaction prevents late T cell costimulatory signaling. Prevents development of autoimmune and inflammatory disease in preclinical models.