The melanoma cell-Tim-3 receptor binds Galectin-9 and suppresses MAPK signaling to inhibit tumor growth (black, solid line). Ab-based melanoma-Tim-3 blockade (red, solid line) activates MAPK effectors, MEK and ERK, thereby unintentionally promoting tumorigenesis (red, dashed lines). Combination therapy with MEK inhibitors (MEKi) reverses Tim-3 Ab-mediated MEK activation (green, solid line), leading to desirable melanoma growth suppression (green, dashed line).