Tumor necrosis factor receptor superfamily member 18 (GITR) (GITR)

Tumor necrosis factor receptor superfamily member 18 (GITR) is a type I transmembrane protein that functions as a costimulatory immune checkpoint receptor [UniProt: Q9Y275]. It is constitutively expressed at high levels on regulatory T cells (Tregs) and is rapidly upregulated on effector CD4+ and CD8+ T cells following TCR activation [PubMed: 28811304]. GITR signaling, typically triggered by its ligand GITRL, enhances T-cell proliferation, cytokine production, and survival, while simultaneously impairing the suppressive function of Tregs [NCBI: 8784]. In the context of oncology, GITR is a prominent therapeutic target because its activation can overcome tumor-induced immunosuppression and promote a robust anti-tumor immune response [PubMed: 30610167]. Therapeutic strategies primarily involve agonistic monoclonal antibodies designed to trigger the receptor, often investigated in combination with PD-1/PD-L1 inhibitors to achieve synergistic clinical effects [ClinicalTrials.gov]. Despite its potential, clinical development faces challenges such as suboptimal monotherapy activity and the need for precise dosing to avoid immune-related toxicities [PubMed: 31434690].

Other names

Glucocorticoid-induced TNFR-related proteinCD357Activation-inducible TNFR-related proteinAITRTNFRSF18

Agonism of the GITR receptor to enhance effector T-cell activity and reduce regulatory T-cell mediated immunosuppression.