2026-04-14 京都大学
高脂肪食給餌による代謝ストレスは、代謝ストレスを取り除いた後もCD8⁺ T細胞の脂質構成の変化として長期間にわたって残存し、細胞死の一種であるフェロプトーシスへの感受性を持続的に上昇させてがんに対する免疫応答を減弱させている。CD8⁺ T細胞はキサンチンから抗酸化作用を有するBH4を産生することでフェロプトーシス抵抗性を獲得している。（BioRender で作成。作者：但馬正樹）
＜関連情報＞
- https://www.kyoto-u.ac.jp/ja/research-news/2026-04-14
- https://www.kyoto-u.ac.jp/sites/default/files/2026-04/web_2604_Tajima-e9f5e451606450532a70c5d760ec44af.pdf
- https://www.nature.com/articles/s41590-026-02491-w
プリンサルベージ経路はCD8 + T細胞を代謝ストレスから保護する Purine salvage pathway protects CD8+ T cells from metabolic stress
Masaki Tajima,He Hao,Baihao Zhang,Yuta Matsuoka,Kazuhiro Sonomura,Koshi Imami,Yosuke Isobe,Rae Maeda,Yu-Hsien Lin,Akihiro Shimba,Ryoma Kato,Pedro Henrique Costa Cruz,Sayaka Washizu,Yosuke Ikejiri,Akiyo Morinibu,Clive Steven Barker,Jun Seita,Yibo Wu,Satomi Ito,Seiko Narushima,Rei Nakano,Mikako Maruya,Wakana Kobayashi,Sai Shanmukha Priya Narayanan,… Sidonia Fagarasan
Nature Immunology Published:13 April 2026
DOI:https://doi.org/10.1038/s41590-026-02491-w
Abstract
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.
