Mogat1 drives metabolic adaptations to evade immune surveillance

Huan Wei, Congyi Niu, Yue Shi, Yingfei Fang, Chengheng Yang, Jian Liu and Zhenjie Xu ()
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Huan Wei: Fudan University
Congyi Niu: Fudan University
Yue Shi: School of Life Sciences, Fudan University
Yingfei Fang: Westlake University
Chengheng Yang: Westlake University
Jian Liu: Westlake University
Zhenjie Xu: Westlake University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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 resistance and suggesting reduced reliance on conventional antigen presentation. Our findings reveal a lipid metabolism-centered immune evasion mechanism and highlight Mogat1 as a potential target to improve cancer immunotherapy.

Date: 2025
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DOI: 10.1038/s41467-025-62134-w

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