Ex vivo: When cholesterol levels in CD8+ T cells were low, there was an improvement in inhibitory receptors related to T cell exhaustion (PD-1, TIM-3, LAG-3, 2B4); apoptosis was reduced; migration was improved; OXPHOS and glycolysis increased; and the anti-tumor activity was restored as measured by granzyme B, IFN-γ and TNF-α production in CD8+ T cells. In vivo: CD8+ TIL from shRNA-treated cancer cells against Hmgcr, or with simvastatin, had lower PD-1 and 2B4 expression, and less cholesterol content, with better anti-tumor activity. Here, GZMB is linked to cancer.