In addition, albeit less potently than SK1 silencing, pharmacological inhibition of SK1 by SKI-I9 significantly improved the anti-CTLA-4 therapy on established Yumm melanoma, and led to a potent increase of tumor rejection and animal survival (Fig. 5d, e), as well as CD8/Treg ratio (Fig. 5f). This evidence concerns the gene CTLA4 and melanoma.