近日，广州大学教授王雄军及其团队报道了5-磷酸木糖糖促进祖细胞样衰竭SLC35E2⁺ CD8⁺ T效应细胞的持续抗肿瘤活性。相关论文于2025年7月17日发表在《细胞—代谢》杂志上。

在体内代谢CRISPR/Cas9基因敲除筛选中，研究人员发现木糖激酶（XYLB）是一种肿瘤抑制因子，通过产生木糖5-磷酸（Xu5P）来损害肺定植，从而促进CD8⁺ T细胞的细胞毒性。从机制上说，CD8⁺ T细胞表达相对较高水平的溶质载体家族35成员E2 (SLC35E2)，这是植物Xu5P转运蛋白的同源物，促进Xu5P的摄取，随后加强五糖磷酸途径和糖酵解，以实现能量/氧化还原平衡。

此外，该课题组人员发现Xu5P通过TET甲基胞嘧啶双加氧酶3 （TET3）介导的Tcf7启动子的DNA去甲基化，促进Xu5P应答的祖细胞样SLC35E2⁺ CD8⁺衰竭T细胞，从而增强CD8⁺ T细胞应答。在临床上，XYLB或血Xu5P升高与CD8⁺ T细胞疗效增强和转移减少相关。在小鼠模型中，补充或采用富含Xu5P的饮食可与抗PD-1治疗协同增强抗肿瘤免疫。这些发现为饮食干预转移性癌症的可能性提供了见解。

据了解，参与肿瘤转移和免疫逃避的代谢适应值得研究。

附：英文原文

Title: Xylulose 5-phosphate fosters sustained antitumor activity of progenitor-like exhausted SLC35E2+ CD8+ T effector cells

Author: Tiezhu Shi, Jialiang Shao, Yufeng Ding, Hong Tang, Xiangyin Tan, Sisi Zhou, Shaoqing Yu, Xiang Wang, Guanzhen Yu, Ninghan Feng, Xiongjun Wang

Issue&Volume: 2025-07-17

Abstract: Metabolic adaptations involved in tumor metastasis and immune evasion merit investigation. Here, using in vivo metabolic CRISPR/Cas9 knockout screening, we identified xylulokinase (XYLB) as a tumor suppressor that impairs lung colonialization by producing xylulose 5-phosphate (Xu5P), which promotes CD8+ T cell cytotoxicity. Mechanistically, CD8+ T cells express relatively high levels of solute carrier family 35 member E2 (SLC35E2), a homolog of the plant Xu5P transporter, to facilitate Xu5P uptake and subsequently intensify the pentose phosphate pathway and glycolysis for energy/redox balance. Furthermore, we revealed that Xu5P potentiates CD8+ T cell response by promoting Xu5P-responsive progenitor-like SLC35E2+ CD8+ exhausted T cells via tet methylcytosine dioxygenase 3 (TET3)-mediated DNA demethylation of the Tcf7 promoter. Clinically, elevated XYLB or blood Xu5P correlates with enhanced CD8+ T cell efficacy and reduced metastasis. In murine models, Xu5P supplementation or adopting Xu5P-rich diets synergizes with anti-PD-1 therapy to enhance antitumor immunity. These findings offer insights into the potentiality of dietary interventions for metastatic cancer.

DOI: 10.1016/j.cmet.2025.06.011

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00324-9