Mogat1 drives metabolic adaptations to evade immune surveillance.

ABSTRACT: Immune checkpoint blockade (ICB) therapies for solid tumors often fail due to resistance, necessitating new strategies. While efforts target IFNγ signaling or antigen presentation, other immune evasion mechanisms are unclear. Here, we identify Monoacylglycerol O-Acyltransferase 1 (Mogat1) as a critical modulator of tumor immune evasion using an in vivo transcriptomic screen in progressing tumors. We find that tumors exploit Mogat1 to sequester fatty acids into triglycerides, a metabolic adaptation that fuels growth and fosters an immunosuppressive microenvironment, enabling immune escape. Genetic inhibition of Mogat1 suppresses tumor growth by promoting T-cell infiltration and enhancing their tumor-killing ability. Importantly, Mogat1 loss sensitizes tumors to PD-1 blockade, overcoming res

SUBMITTER: Wei H 

PROVIDER: S-EPMC12314084 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature