EIF4E Enriched Extracellular Vesicles Induce Immunosuppressive Macrophages through HMGCR-Mediated Metabolic Rewiring.

ABSTRACT: Tumor driven immune suppression poses a significant impediment to the success of immunotherapy in ovarian cancer. Among the various mechanisms contributing to immune suppression, intracellular communication facilitated by tumor-derived extracellular vesicles (EVs) within the tumor microenvironment emerges as a pivotal factor influencing tumor growth. Here, it is demonstrated that extracellular vesicle-packaged eIF4E from tumor cells alters protein translation in macrophages, contributing to antitumor immune response. Mechanistically, tumor derived EV-packaged eIF4E significantly enhances the expression of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), driving the synthesis and secretion of cholesterol. This, in turn, activates macrophages and causes immunosuppression through the

SUBMITTER: Mittal S 

PROVIDER: S-EPMC12622447 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature