T 细胞在抗肿瘤反应中发挥核心作用。然而，它们经常在肿瘤微环境中面临许多障碍，包括缺乏可用的必需代谢物，如葡萄糖和氨基酸。此外，癌细胞可以通过上调代谢物转运蛋白并维持高代谢率来垄断这些资源，从而繁荣和增殖，从而在竞争中胜过T细胞。在此，我们试图通过增强T细胞的糖酵解能力来更好地改善肿瘤附近的T细胞抗肿瘤功能。与肿瘤细胞竞争。为了实现这一目标，我们对人类 T 细胞进行了改造，使其表达一种关键的糖酵解酶——磷酸果糖激酶，并结合葡萄糖转运蛋白 3（一种葡萄糖转运蛋白）。我们将它们与肿瘤特异性嵌合抗原或 T 细胞受体一起共表达。与对照细胞相比，工程细胞表现出细胞因子分泌增加和 T 细胞激活标记物上调。此外，它们表现出卓越的糖酵解能力，这在人类肿瘤异种移植模型中转化为改善的体内治疗潜力。总之，这些发现支持实施 T 细胞代谢工程以增强癌症细胞免疫疗法的功效。©作者（或其雇主）2024。根据 CC BY-NC 允许重复使用。不得商业再利用。请参阅权利和权限。英国医学杂志出版。

T cells play a central role in the antitumor response. However, they often face numerous hurdles in the tumor microenvironment, including the scarcity of available essential metabolites such as glucose and amino acids. Moreover, cancer cells can monopolize these resources to thrive and proliferate by upregulating metabolite transporters and maintaining a high metabolic rate, thereby outcompeting T cells.Herein, we sought to improve T-cell antitumor function in the tumor vicinity by enhancing their glycolytic capacity to better compete with tumor cells. To achieve this, we engineered human T cells to express a key glycolysis enzyme, phosphofructokinase, in conjunction with Glucose transporter 3, a glucose transporter. We co-expressed these, along with tumor-specific chimeric antigen or T-cell receptors.Engineered cells demonstrated an increased cytokine secretion and upregulation of T-cell activation markers compared with control cells. Moreover, they displayed superior glycolytic capacity, which translated into an improved in vivo therapeutic potential in a xenograft model of human tumors.In summary, these findings support the implementation of T-cell metabolic engineering to enhance the efficacy of cellular immunotherapies for cancer.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.