TNFRSF18 (also known as GITR - glucocorticoid-induced tumor necrosis factor receptor-related protein) is a cell surface receptor that plays critical roles in T cell regulation and immune responses. The receptor is highly expressed on regulatory T cells (Tregs) and exhausted CD8+ T cells, where it serves as a key marker of immunosuppressive cellular states 1 2. TNFRSF18 mediates NF-κB activation and promotes proliferative programs in immune cells, particularly in the most highly suppressive subset of tumor-infiltrating Tregs (OX40hiGITRhi) that correlates with resistance to PD-1 blockade immunotherapy 1. In the tumor microenvironment, TNFRSF18 expression is elevated in exhausted CD8+ T cells and serves as a novel biomarker for T cell dysfunction across cancer progression 2 3. The receptor also functions in macrophages, where it exacerbates inflammatory responses by regulating NLRP3 inflammasome activation through post-translational modifications, contributing to sepsis pathology 4. Therapeutically, TNFRSF18 represents a promising target for cancer immunotherapy, with agonistic antibodies showing synergistic antitumor activity when combined with other immunotherapeutic approaches 5 6. The receptor's expression pattern across different immune cell subsets makes it both a valuable prognostic biomarker and a potential therapeutic target in multiple disease contexts.