Dietary fructose-mediated adipocyte metabolism drives antitumor CD8 + T cell responses

Fructose consumption is associated with tumor growth and metastasis in mice, yet its impact on antitumor immune responses remains unclear. Here, we show that dietary fructose modulates adipocyte metabolism to enhance antitumor CD8 T cell immune responses and control tumor growth. Transcriptional pro...

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Bibliographic Details
Published in:Cell metabolism 2023-12, Vol.35 (12), p.2107-2118.e6
Main Authors: Zhang, Yuerong, Yu, Xiaoyan, Bao, Rujuan, Huang, Haiyan, Gu, Chuanjia, Lv, Qianming, Han, Qiaoqiao, Du, Xian, Zhao, Xu-Yun, Ye, Youqiong, Zhao, Ren, Sun, Jiayuan, Zou, Qiang
Format: Article
Language:English
Subjects:
Animals
CD8-Positive T-Lymphocytes
Humans
Immunotherapy
Leptin - metabolism
Lymphocyte Activation
Mice
Neoplasms - metabolism
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Summary:Fructose consumption is associated with tumor growth and metastasis in mice, yet its impact on antitumor immune responses remains unclear. Here, we show that dietary fructose modulates adipocyte metabolism to enhance antitumor CD8 T cell immune responses and control tumor growth. Transcriptional profiling of tumor-infiltrating CD8 T cells reveals that dietary fructose mediates attenuated transition of CD8 T cells to terminal exhaustion, leading to a superior antitumor efficacy. High-fructose feeding initiates adipocyte-derived leptin production in an mTORC1-dependent manner, thereby triggering leptin-boosted antitumor CD8 T cell responses. Importantly, high plasma leptin levels are correlated with elevated plasma fructose concentrations and improved antitumor CD8 T cell responses in patients with lung cancer. Our study characterizes a critical role for dietary fructose in shaping adipocyte metabolism to prime antitumor CD8 T cell responses and highlights that the fructose-leptin axis may be harnessed for cancer immunotherapy.
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2023.09.011