小柯机器人

上海交通大学医学院邹强等研究人员合作发现，膳食果糖介导的脂肪细胞代谢驱动抗肿瘤CD8⁺ T细胞反应。这一研究成果于2023年10月19日在线发表在国际学术期刊《细胞—代谢》上。

研究人员发现膳食果糖能调节脂肪细胞的新陈代谢，从而增强CD8⁺ T细胞的抗肿瘤免疫反应并控制肿瘤生长。肿瘤浸润CD8⁺ T细胞的转录谱分析显示，膳食果糖介导CD8⁺ T细胞向终末衰竭的过渡减少，从而产生卓越的抗肿瘤疗效。高果糖喂养以一种依赖于mTORC1的方式启动脂肪细胞源性瘦素的产生，从而引发瘦素增强的抗肿瘤CD8⁺ T细胞反应。

重要的是，在肺癌患者中，高血浆瘦素水平与血浆果糖浓度升高和抗肿瘤CD8⁺ T细胞反应改善相关。这项研究描述了膳食果糖在塑造脂肪细胞代谢以增强抗肿瘤CD8⁺ T细胞反应中的关键作用，并强调了果糖-瘦素轴可用于癌症免疫疗法。

据介绍，果糖摄入与小鼠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。

附：英文原文

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

Author: 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

Issue&Volume: 2023-10-19

Abstract: Fructose consumption is associated with tumor growth and metastasis in mice, yet itsimpact on antitumor immune responses remains unclear. Here, we show that dietary fructosemodulates adipocyte metabolism to enhance antitumor CD8+ T cell immune responses and control tumor growth. Transcriptional profiling of tumor-infiltratingCD8+ T cells reveals that dietary fructose mediates attenuated transition of CD8+ T cells to terminal exhaustion, leading to a superior antitumor efficacy. High-fructosefeeding 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 elevatedplasma fructose concentrations and improved antitumor CD8+ T cell responses in patients with lung cancer. Our study characterizes a criticalrole for dietary fructose in shaping adipocyte metabolism to prime antitumor CD8+ T cell responses and highlights that the fructose-leptin axis may be harnessed forcancer immunotherapy.

DOI: 10.1016/j.cmet.2023.09.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00367-4

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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