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DGAT1 mediates sex-specific CD8+ T cell antitumour responses

Fatty acid (FA) oxidation plays an important role in T cell responses. However, whether DGAT1-mediated FA esterification to triacylglycerol also regulates T cell function remains unclear. Here we uncover a sexually dimorphic requirement for DGAT1 expression in CD8+ tumour-infiltrating lymphocyte fun...

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Main Authors: Madi, Alaa (Author) , Shi, Hui (Author) , Su, Min (Author) , Mady, Ahmed (Author) , Lv, Boqiong (Author) , Wang, Haiyan (Author) , Yang, Bing (Author) , Yan, Zhenni (Author) , Jin, Xiaomeng (Author) , Wu, Lingling (Author) , Lv, Mengyue (Author) , Hering, Marvin (Author) , Ma, Sicong (Author) , Mieg, Alessa (Author) , Zettl, Ferdinand (Author) , Yan, Xin (Author) , Mohr, Kerstin (Author) , Knabe, Nora (Author) , Poschet, Gernot (Author) , Richter, Karsten (Author) , Schleußner, Nikolai (Author) , Jackstadt, René-Filip (Author) , Loges, Sonja (Author) , Papavasiliou, Nina (Author) , Wang, Xi (Author) , Wu, Jingxia (Author) , Cui, Guoliang (Author)
Format: Article (Journal)
Language:English
Published: March 2026
In: Nature metabolism
Year: 2026, Volume: 8, Issue: 3, Pages: 685-703
ISSN:2522-5812
DOI:10.1038/s42255-026-01462-7
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1038/s42255-026-01462-7
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s42255-026-01462-7
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Author Notes:Alaa Madi, Hui Shi, Min Su, Ahmed Mady, Boqiong Lv, Haiyan Wang, Bing Yang, Zhenni Yan, Xiaomeng Jin, Lingling Wu, Mengyue Lv, Marvin Hering, Sicong Ma, Alessa Mieg, Ferdinand Zettl, Xin Yan, Kerstin Mohr, Nora Knabe, Gernot Poschet, Karsten Richter, Nikolai Schleußner, Rene-Filip Jackstadt, Sonja Loges, F. Nina Papavasiliou, Xi Wang, Jingxia Wu, Guoliang Cui
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Summary:Fatty acid (FA) oxidation plays an important role in T cell responses. However, whether DGAT1-mediated FA esterification to triacylglycerol also regulates T cell function remains unclear. Here we uncover a sexually dimorphic requirement for DGAT1 expression in CD8+ tumour-infiltrating lymphocyte function. In female mice, T cell-specific Dgat1 deficiency improves mitochondrial metabolic fitness and expands the pool of progenitor exhausted CD8+ T (Tex) cells to sustain antitumour responses. In male mice, however, Dgat1 deficiency leads to FA peroxidation, endoplasmic reticulum (ER) stress and CD8+ Tex cell death. We show that these effects are mediated by androgen receptor (AR) signalling. Deletion of Ar, overexpression of glutathione peroxidase 4, or inhibition of ER stress-induced cell death rescues Dgat1-deficient CD8+ T cell survival and promotes antitumour responses in male mice. Overall, this study suggests that DGAT1 detoxifies AR signalling in male mice to protect against ER stress-induced cell death and maintain T cell stemness, and uncovers sex-specific metabolic adaptations in the tumour microenvironment.
Item Description:Im Titel ist das Pluszeichen hochgestellt
Online veröffentlicht am: 20. März 2026
Gesehen am 24.08.2026
Physical Description:Online Resource
ISSN:2522-5812
DOI:10.1038/s42255-026-01462-7

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