癌症对维生素B2的竞争为T细胞凋亡创造了代谢检查点，这一成果由广州医科大学边英杰课题组经过不懈努力而取得。相关论文于2026年10月6日发表在《细胞》杂志上。

肿瘤与T细胞之间的代谢竞争驱动免疫逃逸，但其转运蛋白和机制在很大程度上仍不清楚。在此，研究人员建立了CareSLCs平台，并鉴定出SLC52A3介导的维生素B2（VB2）摄取对T细胞抗肿瘤免疫不可或缺。机制上，VB2缺乏损害线粒体呼吸和谷胱甘肽再生，导致线粒体自噬、不稳定铁积累和脂质过氧化，从而触发T细胞铁死亡。出乎意料的是，肿瘤优先使用SLC52A2而非SLC52A3来清除VB2并竞争性胜过T细胞。在免疫健全宿主体内敲除肿瘤SLC52A2可增强T细胞功能，而不明显影响肿瘤内在生长。临床上，肿瘤SLC52A2高表达与T细胞功能障碍和生存期差相关，而膳食VB2摄入与癌症风险降低相关。因此，补充VB2或过表达SLC52A3可增强CAR-T细胞的抗肿瘤疗效。研究结果表明，肿瘤对VB2的竞争建立了一个驱动T细胞铁死亡的代谢检查点，而增强VB2摄取可重新激活T细胞以改善癌症免疫治疗。

附：英文原文

Title: Cancer competition for vitamin B2 creates metabolic checkpoint for T cell ferroptosis

Author: Huanpeng Chen, Chao Li, Yujing Ke, Zilong Wu, Ziwei Ou, Nanqi Huang, Zhenyu Lin, Huixin Gao, Xuehu Xu, Lijuan Lu, Zhaofeng Huang, Yingjie Bian

Issue&Volume: 2026-10-06

Abstract: Metabolic competition between tumors and T cells drives immune evasion, but the transporters and mechanisms remain largely elusive. Here, we establish the CareSLCs platform and identify that SLC52A3-mediated vitamin B2 (VB2) uptake is indispensable for T cell antitumor immunity. Mechanistically, VB2 deficiency impairs mitochondrial respiration and glutathione regeneration, leading to mitophagy, labile iron accumulation, and lipid peroxidation that trigger T cell ferroptosis. Unexpectedly, tumors preferentially employ SLC52A2, not SLC52A3, to scavenge VB2 and outcompete T cells. Tumor SLC52A2 ablation enhances T cell function in immunocompetent hosts without appreciably affecting intrinsic tumor growth. Clinically, high tumoral SLC52A2 correlates with T cell dysfunction and poor survival, whereas dietary VB2 intake is associated with reduced cancer risks. Thus, VB2 supplementation or SLC52A3 overexpression augments CAR-T cell antitumor efficacy. Our results suggest that tumoral VB2 competition establishes a metabolic checkpoint driving T cell ferroptosis and that enhancing VB2 uptake reinvigorates T cells to improve cancer immunotherapy.

DOI: 10.1016/j.cell.2026.09.020

Source: https://www.cell.com/cell/abstract/S0092-8674(26)01122-0