GITR Ligand/TNFSF18 Trimer His Tag Protein, Human

GITR ligand (GITRL), also known as TNFSF18, AITRL, or TL6, is a member of the tumor necrosis factor superfamily and the cognate ligand of the costimulatory receptor GITR (TNFRSF18/CD357). GITRL is a type II transmembrane glycoprotein whose extracellular region adopts the characteristic TNF homology β-sandwich fold; in humans it assembles predominantly as a homotrimer. Trimeric GITRL engages GITR, inducing receptor clustering and signaling through TRAF2/5–NF-κB and MAPK pathways, while metalloprotease cleavage releases soluble GITRL. GITRL is expressed mainly on dendritic cells, macrophages, B cells, and endothelial cells. It promotes the proliferation, activation, and survival of CD4⁺ and CD8⁺ effector T cells while attenuating regulatory T-cell suppression, placing the GITRL–GITR axis at a central node of antitumor and autoimmune regulation. Clinically, GITR agonist antibodies, multimeric GITRL constructs, anti-PD-1–GITRL bispecific molecules, and GITRL-armored CAR-NK/CAR-T cells are being developed for cancer immunotherapy. Monotherapy has shown limited efficacy in early trials, so combination with PD-1 or CTLA-4 blockade is now the main strategy, with additional potential in autoimmune disease and HIV reservoir reactivation.