| First Author | Shi T | Year | 2025 |
| Journal | Cell Metab | Volume | 37 |
| Issue | 9 | Pages | 1835-1851.e10 |
| PubMed ID | 40680740 | Mgi Jnum | J:371150 |
| Mgi Id | MGI:8236018 | Doi | 10.1016/j.cmet.2025.06.011 |
| Citation | Shi T, et al. (2025) Xylulose 5-phosphate fosters sustained antitumor activity of progenitor-like exhausted SLC35E2(+) CD8(+) T effector cells. Cell Metab |
| abstractText | 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. |
