| First Author | Tajima M | Year | 2026 |
| Journal | Nat Immunol | Volume | 27 |
| Issue | 5 | Pages | 1026-1038 |
| PubMed ID | 41974963 | Mgi Jnum | J:385010 |
| Mgi Id | MGI:8328808 | Doi | 10.1038/s41590-026-02491-w |
| Citation | Tajima M, et al. (2026) Purine salvage pathway protects CD8(+) T cells from metabolic stress. Nat Immunol 27(5):1026-1038 |
| abstractText | Metabolic stress from a high-fat diet (HFD) impairs antitumor immunity through persistent metabolic rewiring, but its effects and long-term impact on CD8(+) T cell metabolism remain unknown. Here, we found that even temporary exposure to a HFD impaired antitumor immunity 10 weeks after reversion to a normal diet. This was due to lasting metabolome changes that included enrichment in phospholipids sensitive to peroxidation and depletion of antioxidants, affecting the survival and function of CD8(+) T cells. Under oxidative stress, CD8(+) T cells utilized the xanthine salvage pathway to produce guanosine triphosphate, enhancing the amount of tetrahydrobiopterin. Xanthine supplementation reduced lipid peroxidation in tumor-draining lymph nodes and improved antitumor immunity in mice previously on a HFD. Our data indicate that metabolic stress in CD8(+) T cells persists long after restoration of a balanced diet, and manifests as vulnerability to ferroptosis, which could be mitigated by replenishing biopterins through the xanthine salvage pathway. |
