The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity

Abstract

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 tumour immunity. Abcg1−/− mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1−/− mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1−/− macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer. ABCG1 transporter pumps cholesterol out of the cell. Here, the authors show that ABCG1-deficient mice have reduced tumour growth due to a switch of the tumour-associated macrophages from a tumour-promoting to tumour-suppressing phenotype, and are protected from the pro-tumorigenic effects of a Western-like diet.