High cholesterol level is seen in TME and positively correlated with CD8+ T cell exhaustion.51 In a murine melanoma model, cholesterol increases endoplasmic reticulum stress, activates X-box binding protein 1 (XBP1), and upregulates PD-1 expression on CD8+ T cells, indicating that the combination of immunotherapy and cholesterol-reducing therapy may have great benefits.96 Strikingly, lipid metabolism promotes the formation of pre-metastatic niche in ovarian cancer. Here, PDCD1 is linked to melanoma.