ICOSLG (inducible T cell costimulator ligand) is a B7 family costimulatory molecule that primarily functions as a ligand for the T-cell receptor ICOS, enhancing T cell proliferation and cytokine secretion 12. Beyond T cells, ICOSLG induces B cell differentiation into plasma cells [UniProt] and is required for proper neutrophil transmigration in endothelial cells 3. Mechanistically, ICOSLG amplifies pattern-recognition receptor signaling through homotypic ICOS-ICOSL interactions on dendritic cells, recruiting adaptor proteins and activating PKC, MAPK, and NF-κB pathways 4. ICOSLG is critical for mucocutaneous immunity; ICOSLG deficiency causes combined immunodeficiency with recurrent respiratory infections and DNA virus susceptibility at epithelial barriers 5. In cancer contexts, ICOSLG shows bidirectional roles: mesenchymal glioblastoma cells express ICOSLG to expand immunosuppressive IL-10-producing T cells, promoting tumor progression 6, while chemotherapy-induced ICOSL+ B cells enhance anti-tumor immunity by favoring effector T cells 7. High ICOSLG expression correlates with improved response to anti-PD-1 immunotherapy with antihistamine premedication in melanoma 8 and is associated with poor prognosis in gastric cancer through enhanced glycolysis 9. These contrasting roles suggest ICOSLG's function is context- and cell-type dependent.