Fatty acid uptake mediated by FABP4 promotes the formation of CD8⁺T cell senescence through lipid peroxidation in the adipocyte-rich microenvironment of Ovarian Cancer.

ABSTRACT: T cell senescence significantly impairs the efficacy of immune checkpoint blockade (ICB) therapy in cancer. Metabolic reprogramming is a crucial factor in T cell senescence in tumor microenvironment (TME). Ovarian cancer (OvCa) patients derive limited benefit from ICB treatment, probably related to T cell senescence. OvCa cells metastasize to the abdominal cavity rich in omental fat and raise ascites, forming a unique TME, adipocyte-rich TME. In this study, we investigated the effects of adipocyte-rich TME on T cell senescence. Using the single-cell RNA sequencing of OvCa and clinical samples, we found that adipocyte-rich TME is strongly associated with the formation of senescence CD8⁺T (CD8⁺Tsen) cells. Mechanistically, adipocyte-derived factors (MATES) and oleic aci

SUBMITTER: Yu C 

PROVIDER: S-EPMC12905430 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature