2. Academic Validation
  3. Dietary fructose-mediated adipocyte metabolism drives antitumor CD8+ T cell responses

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

  • Cell Metab. 2023 Oct 15:S1550-4131(23)00367-4. doi: 10.1016/j.cmet.2023.09.011.
Yuerong Zhang 1,  Xiaoyan Yu 1,  Rujuan Bao 1,  Haiyan Huang 2,  Chuanjia Gu 3,  Qianming Lv 1,  Qiaoqiao Han 1,  Xian Du 1,  Xu-Yun Zhao 4,  Youqiong Ye 5,  Ren Zhao 6,  Jiayuan Sun 7,  Qiang Zou 8
Affiliations

Affiliations

  • 1 Shanghai Chest Hospital & Shanghai Institute of Immunology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
  • 2 Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 3 Department of Respiratory Endoscopy, Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
  • 4 Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 5 Shanghai Chest Hospital & Shanghai Institute of Immunology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: [email protected].
  • 6 Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: [email protected].
  • 7 Department of Respiratory Endoscopy, Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: [email protected].
  • 8 Shanghai Chest Hospital & Shanghai Institute of Immunology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: [email protected].
PMID: 37863051 DOI: 10.1016/j.cmet.2023.09.011
Abstract

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.

Keywords

adipocyte metabolism; antitumor CD8(+) T cell responses; dietary fructose; mTORC1.

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