The Cholesterol Transporter ABCG1 Links Cholesterol Homeostasis and Tumor Immunity

摘要

ATP-binding Cassette Transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here, we demonstrate a role of ABCG1 as a mediator of tumor immunity. Abcg1^−/− mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumor growth in Abcg1^−/− mice is myeloid cell-intrinsic and is associated with a phenotypic shift of the macrophages from a tumor-promoting M2 to a tumor-fighting M1 within the tumor. Abcg1^−/− macrophages exhibit an intrinsic bias toward M1 polarization with increased NF-κB activation and direct cytotoxicity for tumor cells in vitro. Overall, our study demonstrates that absence of ABCG1 inhibits tumor growth through modulation of macrophage function within the tumor and illustrates a link between cholesterol homeostasis and cancer.