膳食果糖介导的脂肪细胞代谢驱动抗肿瘤CD8+T细胞反应。

Cell metabolism Pub Date : 2023-12-05 Epub Date: 2023-10-19 DOI:10.1016/j.cmet.2023.09.011
Yuerong Zhang, Xiaoyan Yu, Rujuan Bao, Haiyan Huang, Chuanjia Gu, Qianming Lv, Qiaoqiao Han, Xian Du, Xu-Yun Zhao, Youqiong Ye, Ren Zhao, Jiayuan Sun, Qiang Zou
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引用次数: 0

摘要

果糖的摄入与小鼠的肿瘤生长和转移有关,但其对抗肿瘤免疫反应的影响尚不清楚。在这里,我们发现膳食果糖调节脂肪细胞代谢,以增强抗肿瘤CD8+T细胞免疫反应并控制肿瘤生长。肿瘤浸润性CD8+T细胞的转录谱分析表明,膳食果糖介导CD8+T淋巴细胞向终末耗竭的减弱过渡,从而产生优异的抗肿瘤功效。高果糖喂养以mTORC1依赖的方式启动脂肪细胞衍生的瘦素的产生,从而触发瘦素增强的抗肿瘤CD8+T细胞反应。重要的是,高血浆瘦素水平与癌症患者血浆果糖浓度升高和抗肿瘤CD8+T细胞反应改善有关。我们的研究表明,膳食果糖在形成脂肪细胞代谢以引发抗肿瘤CD8+T细胞反应中的关键作用,并强调果糖-肽轴可用于癌症免疫疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Dietary fructose-mediated adipocyte metabolism drives antitumor CD8<sup>+</sup> T cell responses.

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 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.

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