机构：[1]Hongqiao International Institute of Medicine, Tongren Hospital & Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[2]Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[3]Department of Nephrology, Affiliated Hospital of Hebei Engineering University, Handan, China.[4]Department of Respiratory Endoscopy and Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[5]Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[6]Department of Liver Surgery and Transplantation and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.[7]Central Laboratory, Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Affiliated Hospital of Hebei University, Baoding, China.河北大学附属医院
Dietary nutrients are inextricably linked to antitumour immune responses. However, the effect of diet-derived galactose on antitumour immunity remains unclear. Here we show that dietary galactose augments CD8+ T cell immunity to suppress tumour progression. High-galactose feeding drives hepatocyte-derived insulin-like growth factor binding protein 1 (IGFBP-1) production, thus restraining IGF-1 signalling-dependent T cell exhaustion. IGF-1 receptor (IGF-1R) deficiency in T cells potentiates antitumour CD8+ T cell responses and phenocopies high-galactose feeding by preventing T cell exhaustion. Circulating galactose reprograms hepatocyte metabolism to inactivate mTORC1, thereby inducing the production of IGFBP-1 to boost CD8+ T cell function. Furthermore, patients with cancer who have high plasma IGFBP-1 levels exhibit blocked T cell exhaustion and enhanced T cell responses in tumour tissues. These findings reveal that dietary galactose specifically elicits potent antitumour CD8+ T cell responses by facilitating hepatocyte-derived IGFBP-1 production, providing insights into the development of more effective immunotherapies against cancers.
基金：
National Natural Science Foundation of China [82225020, 82430054, 82373072]; National Key Research and Development Program of China [2020YFA0803603, 2021YFA1301402]; Natural Science Foundation of Hebei Province [H2022201067]; Central Government Guides Local Science and Technology Development Special Project [236Z7744G]
第一作者机构：[1]Hongqiao International Institute of Medicine, Tongren Hospital & Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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通讯作者：
推荐引用方式(GB/T 7714)：
Du Xian,Li Wenyan,Li Guiying,et al.Diet-derived galactose reprograms hepatocytes to prevent T cell exhaustion and elicit antitumour immunity[J].NATURE CELL BIOLOGY.2025,27(8):doi:10.1038/s41556-025-01716-8.
APA：
Du, Xian,Li, Wenyan,Li, Guiying,Guo, Chenyue,Tang, Xuyi...&Zou, Qiang.(2025).Diet-derived galactose reprograms hepatocytes to prevent T cell exhaustion and elicit antitumour immunity.NATURE CELL BIOLOGY,27,(8)
MLA：
Du, Xian,et al."Diet-derived galactose reprograms hepatocytes to prevent T cell exhaustion and elicit antitumour immunity".NATURE CELL BIOLOGY 27..8(2025)
生物学