代谢工程促进抗肿瘤免疫，这一成果由分子药理学专业Kayvan R. Keshari小组经过不懈努力而取得。2025年2月27日出版的《癌细胞》杂志发表了这项成果。

研究人员发现，在体外葡萄糖限制条件下，表达GLUT5的CD8⁺ T细胞、巨噬细胞和嵌合抗原受体（CAR） T细胞都表现出改善的效应功能。在体外，表达GLUT5的T细胞表现出较高的果糖分解活性，在小鼠和人异种移植模型中表现出更高的抗肿瘤功效，特别是在补充果糖后。总之，他们的数据表明，通过GLUT5的代谢工程使免疫细胞能够有效地利用果糖，并在葡萄糖限制的TME中增强抗肿瘤免疫。

据介绍，西方饮食中的果糖摄入量增加，但其对抗肿瘤免疫的影响尚不清楚。果糖在肝脏和小肠中代谢，在那里果糖转运蛋白被高度表达。大多数肿瘤无法驱动糖酵解通量，使果糖在肿瘤微环境（TME）中富集。免疫细胞可以利用TME中多余的果糖来表达果糖特异性转运体GLUT5，从而增强效应功能。

附：英文原文

Title: Metabolic engineering to facilitate anti-tumor immunity

Author: Tanya Schild, Patrick Wallisch, Yixuan Zhao, Ya-Ting Wang, Lyric Haughton, Rachel Chirayil, Kaitlyn Pierpont, Kevin Chen, Sara Nunes-Violante, Justin Cross, Elisa de Stanchina, Craig B. Thompson, David A. Scheinberg, Justin S.A. Perry, Kayvan R. Keshari

Issue&Volume: 2025-02-27

Abstract: Fructose consumption is elevated in western diets, but its impact on anti-tumor immunity is unclear. Fructose is metabolized in the liver and small intestine, where fructose transporters are highly expressed. Most tumors are unable to drive glycolytic flux using fructose, enriching fructose in the tumor microenvironment (TME). Excess fructose in the TME may be utilized by immune cells to enhance effector functions if engineered to express the fructose-specific transporter GLUT5. Here, we show that GLUT5-expressing CD8⁺ T cells, macrophages, and chimeric antigen receptor (CAR) T cells all demonstrate improved effector functions in glucose-limited conditions in vitro. GLUT5-expressing T cells show high fructolytic activity in vitro and higher anti-tumor efficacy in murine syngeneic and human xenograft models in vivo, especially following fructose supplementation. Together, our data demonstrates that metabolic engineering through GLUT5 enables immune cells to efficiently utilize fructose and boosts anti-tumor immunity in the glucose-limited TME.

DOI: 10.1016/j.ccell.2025.02.004

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00056-X