Reports from University of the Chinese Academy of Sciences Add New Data to Findings in Genomics and Genetics (25-hydroxycholesterol Regulates Lysosome Amp Kinase Activation and Metabolic Reprogramming To Educate Immunosuppressive Macrophages).

A recent report from the University of the Chinese Academy of Sciences in Shanghai, China, explores the role of cholesterol metabolites in the tumor microenvironment and their impact on macrophages. The researchers discovered that the expression of cholesterol-25-hydroxylase (Ch25h) is induced by interleukin-4 (IL-4) and interleukin-13 (IL-13), leading to the accumulation of 25-hydroxycholesterol (25HC). This accumulation of 25HC in lysosomes competes with cholesterol for binding to GPR155, inhibiting the kinase mTORC1 and activating AMPKa, which results in metabolic reprogramming and immunosuppressive macrophages. Targeting Ch25h could enhance anti-tumor efficacy by improving T cell numbers and activation. [Extracted from the article]