Furthermore, ICOSLG has also been shown to induce CD8+ cytotoxic lymphocyte-mediated antitumor response41,42 and induces both Th1 and Th2 cytokine production in a glioma model.37 Reasons for these discrepancies could be: (1) dual and/or tissue specific functions of ICOSLG; (2) secretion of soluble ICOSLG from nontumor cells impacting antitumor immunity; (3) crosstalk between cells in the TME affecting ICOSLG function; and (4) independent functions of membrane-bound, soluble and circulating ICOSLG. Here, ICOSLG is linked to central nervous system cancer.