GITRL

GITRL, or glucocorticoid-induced TNFR-related ligand, is a protein in the tumor necrosis factor (TNF) ligand superfamily that binds to the GITR receptor (TNFRSF18) on T cells. The gene encoding GITRL in humans is TNFSF18. It is part of the signaling axis that modulates T cell–mediated immune responses and is primarily produced by antigen-presenting cells.

GITRL expression is detected mainly on professional antigen-presenting cells such as dendritic cells, B cells, and macrophages, with lower levels on other cell types. The ligand is typically membrane-bound, though a soluble form can be present in certain biological fluids due to proteolytic processing. Expression can be upregulated by inflammatory stimuli, linking GITRL availability to immune activation status.

The binding of GITRL to GITR on T cells provides a co-stimulatory signal that can enhance T cell activation, proliferation, and survival. GITR signaling also influences regulatory T cells, potentially diminishing their suppressive capacity or altering their function to favor effector responses. This axis therefore plays a role in shaping the balance between immune activation and regulation during immune challenges.

Clinically and experimentally, the GITRL–GITR axis has been explored as a target for immunotherapy. Its potential to boost anti-tumor immunity or to modulate autoimmunity and transplant tolerance has led to the development of GITR-agonist strategies and GITRL-based approaches, including combination therapies with other checkpoint inhibitors. Results vary by disease context, underscoring the need for further research to define optimal applications and patient selection.