Targeting cholesterol metabolism in tumor and its immune microenvironment: opportunities and challenges

Cholesterol metabolism provides cell and organelle membrane components, and its precursors and derivatives exert a variety of biological functions. Dysregulated cholesterol metabolism has emerged as a hallmark of tumors. In the tumor microenvironment, cell-intrinsic and cell-extrinsic cues reprogram cholesterol metabolism to drive tumorigenesis and tumor development. Clinical studies and mechanistic investigations into cholesterol metabolism pathways have uncovered novel metabolic vulnerabilities that hold promise for cholesterol metabolism-targeted therapies for cancer. Moreover, recent studies highlight that manipulating cholesterol metabolism could reshape the immunological landscape and re-boost anti-tumor immunity. Thus, it is critical to deeply discuss the role of cholesterol metabolism in tumors and immune microenvironment to extend this knowledge into current immunotherapies. In this review, we summarize current insights into reprogrammed cholesterol metabolism in tumors and explore the complex interplay between cholesterol metabolism and anti-tumor immunity in diverse immune components within the tumor microenvironment. These findings may provide novel clinical strategies for targeting cholesterol metabolism in the context of cancers.