9-PAHSA orchestrates TCR-T cell fate to boost anti-tumor immunity

ABSTRACT: This study reveals endogenous lipid 9-PAHSA strongly enhances T cell stemness and migration properties. Spatially resolved multi-omics analyses in mouse models and clinical samples solidified this regulatory correlation. Mechanically, ICAM2 acts as a cell surface receptor sensing 9-PAHSA. The activated ICAM2-Ezrin signaling cascade promotes FOXO1 nuclear translocation, further initiating stemness-related transcriptional profiles. Based on this mechanism, we constructed ICAM2-overexpressing engineered TCR-T cells. Such modified cells exert potent anti-tumor effects, meanwhile triggering sustained systemic anti-tumor immune reactivity. This finding uncovers a metabolic sensing regulatory pattern in T cells, and offers a promising strategy to optimize cell immunotherapy against refractory malignancies.

ORGANISM(S): Mus musculus

PROVIDER: GSE315828 | GEO | 2026/01/14

REPOSITORIES: GEO