Glucocorticoid-induced TNFR-related protein (GITR) (GITR)

Glucocorticoid-induced TNFR-related protein (GITR), also known as TNFRSF18, is a co-stimulatory immune checkpoint receptor belonging to the tumor necrosis factor receptor superfamily (UniProt Q99948). It is constitutively expressed at high levels on regulatory T cells (Tregs) and is rapidly upregulated on activated effector T cells, including CD4+ and CD8+ T cells, following T-cell receptor engagement (PMID: 29438008). The interaction between GITR and its ligand (GITRL) at the molecular interface triggers downstream signaling through the NF-kappaB and MAPK pathways, which promotes T-cell expansion, enhances cytokine production, and renders effector T cells resistant to Treg-mediated suppression (PMID: 26063437). In oncology, the GITR/GITRL interface is a major target for immunotherapy, where agonistic monoclonal antibodies are employed to stimulate a robust anti-tumor immune response by activating effector T cells and depleting or attenuating the suppressive activity of Tregs within the tumor microenvironment (PMID: 30635339). While early clinical trials have demonstrated a manageable safety profile, the focus of development has shifted toward combination strategies with PD-1/PD-L1 inhibitors to overcome primary resistance in solid tumors (ClinicalTrials.gov).

Other names

Tumor necrosis factor receptor superfamily member 18TNFRSF18CD357Activation-inducible TNFR-related proteinAITRGITR-D

Agonism of the GITR receptor to enhance effector T-cell activity and survival while simultaneously inhibiting the suppressive function of regulatory T cells.