Cholesterol Metabolism as a Potential Therapeutic Target and a Prognostic Biomarker for Cancer Immunotherapy

Checkpoint-based immunotherapies, such as programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors, have shown promising clinical outcomes in many types of cancers. Unfortunately, the response rate of immune checkpoint inhibitors is low. It is very important to discover novel therapeutic targets and prognostic biomarkers. Cholesterol metabolism has been demonstrated to be related to the occurrence and development of a variety of tumors and may provide a new breakthrough in the development of immunotherapy. First of all, cholesterol metabolism in the tumor microenvironment affects the function of tumor-infiltrating immune cells. In addition, intracellular cholesterol homeostasis is an important regulator of immune cell function. Furthermore, drugs that act on cholesterol metabolism affect the efficacy of immunotherapy. What is more, peripheral blood cholesterol level can be a biomarker to predict the efficacy of immunotherapy. In this review, we aimed to explore the potential role of cholesterol metabolism on immunotherapy. By summarizing the major findings of recent preclinical and clinical studies on cholesterol metabolism in immunotherapy, we suggested that cholesterol metabolism could be a potential therapeutic target and a prognostic biomarker for immunotherapy.