RORγ Bridges Cancer-Driven Lipid Dysmetabolism and Myeloid Immunosuppression.

ABSTRACT: Despite well-documented metabolic and hematopoietic alterations during tumor development, the mechanisms underlying this crucial immunometabolic intersection remain elusive. Of particular interest is the connection between lipid metabolism and the retinoic acid-related orphan receptor (RORC1/RORγ), whose transcriptional activity modulates cancer-related emergency myelopoiesis and is boosted by cholesterol metabolites, whereas hypercholesterolemia itself is associated with dysregulated myelopoiesis. In this study, we show that cancer and hypercholesterolemic diet independently or cooperatively activate RORγ-dependent expansion of myeloid-derived suppressor cells (MDSC) and M2-polarized tumor-associated macrophages (TAM), supporting cancer spread. Moreover, we report that tumor-induced expre

SUBMITTER: Bleve A 

PROVIDER: S-EPMC12223513 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature