Enhanced anti-liver tumor efficacy of chimeric antigen receptor-T cells via SATB1 modulation.

ABSTRACT: Although Chimeric antigen receptor (CAR) T-cell therapy has achieved remarkable success in treating hematopoietic malignancies, its clinical application in solid tumors is profoundly hindered by persistent T-cell exhaustion within the immunosuppressive tumor microenvironment (TME). Here, we identified SATB1-a genome organizer regulating chromatin architecture-as a key suppressor of CAR-T cell exhaustion. In Glypican-3 (GPC3)-targeted CAR-T cells, SATB1 was significantly downregulated in tumor-infiltrating exhausted populations. SATB1 overexpression not only reduced expression of multiple inhibitory receptors (PD-1, CTLA-4, TIM3, and LAG-3) but also promoted a central memory phenotype, enhancing cytokine production and cytotoxicity against hepatocellular carcinoma (HCC) cells in vitro. In v

SUBMITTER: Zhang L 

PROVIDER: S-EPMC12830387 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature