Glucocorticoid-induced TNFR-related gene (GITR) as a therapeutic target for immunotherapy

Abstract

Triggering of the glucocorticoid-induced TNFR-related gene (GITR) increases the activation of T lymphocytes and other immune system cells; furthermore, its ligand, GITRL, delivers signals in the cells where it is expressed. Areas covered: This review describes the effects of GITR/GITRL triggering/inhibition in conventional T cells, regulatory T cells (Tregs), monocytes/macrophages, endothelial cells and other cells of the immune system. GITR triggering appears to be an approach for promoting tumor rejection, treating infection and boosting vaccinations in several murine models. GITR inhibition may be useful for inhibiting inflammation and autoimmune disease development. Expert opinion: The exciting antitumor activity of anti-GITR mAbs depends on CD8⁺ effector T cell activation and inhibition/deletion of tumor-infiltrating Tregs. Whether one of these effects is more relevant is still under debate. Inhibition of GITR triggering plays an interesting anti-inflammatory role, but the potential effect of long-term treatment is to be investigated. The use of adjuvants able to trigger GITR is promising regarding new vaccines. Finally, caution is recommended when translating the findings of experimental murine models to human diseases; biologicals modulating human GITR/GITRL system can behave differently from those modulating the murine GITR/GITRL system.

Keywords: Anti-GITR monoclonal antibodies; GITR fusion proteins; T cell co-stimulation; regulatory T cells (Treg cells); treatment of autoimmune diseases; treatment of cancers; treatment of infection; treatment of inflammatory diseases; vaccination.