Du Xian, Li Wenyan, Li Guiying, Guo Chenyue, Tang Xuyi, Bao Rujuan, Li Runchang, Huang Haiyan, Xu Shuiyu, Yu Xiaoyan, Han Qiaoqiao, Wan Jie, Li Song, Sun Jiayuan, Zhao Ren, Ye Youqiong, Gao Qiang, Ni Zhi-Yu, Cui Xingang, Zou Qiang
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.
Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nat Cell Biol. 2025 Aug 8. doi: 10.1038/s41556-025-01716-8.
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.
膳食营养素与抗肿瘤免疫反应有着千丝万缕的联系。然而，饮食来源的半乳糖对抗肿瘤免疫的影响仍不清楚。在此，我们表明膳食半乳糖可增强CD8 T细胞免疫以抑制肿瘤进展。高半乳糖喂养驱动肝细胞衍生的胰岛素样生长因子结合蛋白1（IGFBP-1）的产生，从而抑制IGF-1信号依赖性T细胞耗竭。T细胞中的IGF-1受体（IGF-1R）缺陷通过防止T细胞耗竭增强抗肿瘤CD8 T细胞反应并模拟高半乳糖喂养。循环半乳糖重新编程肝细胞代谢以失活mTORC1，从而诱导IGFBP-1的产生以增强CD8 T细胞功能。此外，血浆IGFBP-1水平高的癌症患者在肿瘤组织中表现出T细胞耗竭受阻和T细胞反应增强。这些发现表明，膳食半乳糖通过促进肝细胞衍生的IGFBP-1的产生，特异性地引发强大的抗肿瘤CD8 T细胞反应，为开发更有效的癌症免疫疗法提供了思路。
