Glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL)

Glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL) is a member of the tumor necrosis factor (TNF) ligand superfamily (TNFSF18) that binds to its receptor GITR (TNFRSF18, CD357), which is expressed on regulatory and effector T cells. GITRL is primarily expressed on antigen-presenting cells, such as dendritic cells, macrophages, and B cells, and its engagement with GITR provides a potent costimulatory signal for T cell activation. Structural studies indicate that GITRL forms oligomeric states (dimers, trimers, and higher-order clusters) which determine functional signaling potency through GITR. This ligand–receptor pathway plays critical roles in modulating immune responses in cancer, inflammation, and infectious diseases. The GITR/GITRL axis is a focus of therapeutic interest, especially for cancer immunotherapy, due to its ability to boost effector T cell responses and modulate regulatory T cell (Treg) activity

Other names

Tumor necrosis factor ligand superfamily member 18TNFSF18GITR ligandAITR ligand

Agonist antibodies and ligands stimulate the GITR receptor by clustering, leading to activation of effector T cells and abrogation of regulatory T cell suppression. Enhancement of T cell proliferation, survival, and cytokine production. In tumor settings: promoting anti-tumor immunity by enhancing effector T cell activation and reducing Treg-mediated suppression