2. Academic Validation
  3. Diet-derived galactose reprograms hepatocytes to prevent T cell exhaustion and elicit antitumour immunity

Diet-derived galactose reprograms hepatocytes to prevent T cell exhaustion and elicit antitumour immunity

  • Nat Cell Biol. 2025 Aug;27(8):1357-1366. doi: 10.1038/s41556-025-01716-8.
Xian Du # 1,  Wenyan Li # 2,  Guiying Li # 3,  Chenyue Guo # 1,  Xuyi Tang 1,  Rujuan Bao 1,  Runchang Li 4,  Haiyan Huang 5,  Shuiyu Xu 5,  Xiaoyan Yu 1,  Qiaoqiao Han 1,  Jie Wan 1,  Song Li 1,  Jiayuan Sun 4,  Ren Zhao 5,  Youqiong Ye 1,  Qiang Gao 6,  Zhi-Yu Ni 7,  Xingang Cui 8,  Qiang Zou 9
Affiliations

Affiliations

  • 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. gaoqiang@fudan.edu.cn.
  • 7 Central Laboratory, Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Affiliated Hospital of Hebei University, Baoding, China. nizhiyu@hbu.edu.cn.
  • 8 Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. cuixingang@xinhuamed.com.cn.
  • 9 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. Qzou1984@sjtu.edu.cn.
  • # Contributed equally.
PMID: 40781141 DOI: 10.1038/s41556-025-01716-8
Abstract

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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z