日本京都大学Sidonia Fagarasan团队近日取得一项新成果。经过不懈努力，他们的最新研究揭示了嘌呤挽救途径保护CD8⁺ T细胞免受代谢应激。相关论文于2026年4月13日发表在《自然—免疫学》杂志上。

该课题组人员发现，在恢复正常饮食10周后，即使暂时暴露于HFD也会损害抗肿瘤免疫。这是由于持续的代谢组变化，包括对过氧化敏感的磷脂的富集和抗氧化剂的消耗，影响了CD8⁺ T细胞的存活和功能。氧化应激下，CD8⁺ T细胞利用黄嘌呤回收途径产生三磷酸鸟苷，增加四氢生物蝶呤的数量。黄嘌呤的补充减少了肿瘤引流淋巴结中的脂质过氧化，并提高了小鼠先前在HFD上的抗肿瘤免疫。他们的数据表明，在恢复均衡饮食后，CD8+ T细胞中的代谢应激持续很长时间，并表现为对铁下垂的脆弱性，这可以通过黄嘌呤修复途径补充生物蛋白来缓解。

研究人员表示，来自高脂肪饮食（HFD）的代谢应激通过持续的代谢重组损害抗肿瘤免疫，但其对CD8⁺ T细胞代谢的影响和长期影响尚不清楚。

附：英文原文

Title: Purine salvage pathway protects CD8+ T cells from metabolic stress

Author: Tajima, Masaki, Hao, He, Zhang, Baihao, Matsuoka, Yuta, Sonomura, Kazuhiro, Imami, Koshi, Isobe, Yosuke, Maeda, Rae, Lin, Yu-Hsien, Shimba, Akihiro, Kato, Ryoma, Costa Cruz, Pedro Henrique, Washizu, Sayaka, Ikejiri, Yosuke, Morinibu, Akiyo, Barker, Clive Steven, Seita, Jun, Wu, Yibo, Ito, Satomi, Narushima, Seiko, Nakano, Rei, Maruya, Mikako, Kobayashi, Wakana, Narayanan, Sai Shanmukha Priya, Shaheen, Jumana, Neyama, Hiroyuki, Yamada, Ken-ichi, Arita, Makoto, Sugiura, Yuki, Fagarasan, Sidonia

Issue&Volume: 2026-04-13

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.

DOI: 10.1038/s41590-026-02491-w

Source: https://www.nature.com/articles/s41590-026-02491-w