CD8⁺ effector T (T_E) cell proliferation and cytokine production depends on enhanced glucose metabolism. However, circulating T cells continuously adapt to glucose fluctuations caused by diet and inter-organ metabolite exchange. Here we show that transient glucose restriction (TGR) in activated CD8⁺ T_E cells metabolically primes effector functions and enhances tumour clearance in mice. Tumour-specific TGR CD8⁺ T_E cells co-cultured with tumour spheroids in replete conditions display enhanced effector molecule expression, and adoptive transfer of these cells in a murine lymphoma model leads to greater numbers of immunologically functional circulating donor cells and complete tumour clearance. Mechanistically, T_E cells treated with TGR undergo metabolic remodelling that, after glucose re-exposure, supports enhanced glucose uptake, increased carbon allocation to the pentose phosphate pathway (PPP) and a cellular redox shift towards a more reduced state—all indicators of a more anabolic programme to support their enhanced functionality. Thus, metabolic conditioning could be used to promote efficiency of T-cell products for adoptive cellular therapy.

CD8 ⁺效应 T ( _TE ) 细胞增殖和细胞因子产生依赖于葡萄糖代谢的增强。然而，循环T细胞不断适应饮食和器官间代谢物交换引起的葡萄糖波动。在这里，我们发现激活的 CD8 ⁺ T _E细胞中的瞬时葡萄糖限制 (TGR) 在代谢上启动效应器功能并增强小鼠的肿瘤清除。在充满条件下与肿瘤球体共培养的肿瘤特异性 TGR CD8 ⁺ T _E细胞显示出增强的效应分子表达，并且这些细胞在小鼠淋巴瘤模型中的过继转移导致更多数量的具有免疫功能的循环供体细胞和完全的肿瘤清除。从机制上讲，用 TGR 处理的 T _E细胞经历代谢重塑，在重新暴露于葡萄糖后，支持增强的葡萄糖摄取、增加磷酸戊糖途径 (PPP) 的碳分配以及细胞氧化还原向更还原的状态转变——所有指标都表明更多的合成代谢计划来支持其增强的功能。因此，代谢调节可用于提高 T 细胞产品用于过继性细胞治疗的效率。