一碳单元补充燃料瘤透T细胞,并增加检查点封锁
Xincheng Xu1,2,3,4, Zihong Chen1,2,3,4, Caroline R Bartman1,2,3
1Department of Chemistry, Princeton University.
bioRxiv : the preprint server for biology
|November 14, 2023
概括
瘤和T细胞依赖于de novo purin合成,需要一个碳 (1C) 单位. 补充1C来源的格式增强了抗瘤免疫力,并改善了检查点阻塞疗法.
科学领域:
- 代谢途径 代谢途径
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
背景情况:
- 核酸对于细胞能量和核酸合成至关重要.
- purin 合成通过救援或 de novo 途径发生.
- 一个碳 (1C) 单位是de novo purin合成的关键前体.
研究的目的:
- 量化救援对氨酸核酸新合成的贡献.
- 为了研究增加一碳 (1C) 单位对氨酸合成的影响.
- 探索1C补充剂在抗瘤免疫中的治疗潜力.
主要方法:
- 同位素追踪-质谱法用于追踪核酸合成途径.
- 在瘤细胞和T细胞中氨酸合成的分析 (瘤透与脏).
- 用甲醇作为一种形式的预药物来调节体内1C水平.
主要成果:
- 瘤和瘤透的T细胞优先使用de novo purin合成.
- 1C单位的短缺可以限制抗瘤免疫反应.
- 提高循环中的甲酸盐水平可以增强瘤透T细胞中的纯氨酸合成.
- 口服甲醇可以安全地增加甲酸盐水平,增强抗PD-1疗法,并导致持续的瘤回归.
结论:
- 一个碳 (1C) 代谢是抗瘤免疫的关键检查点.
- 药理学1C补充剂,使用甲醇作为预药物,可以克服代谢限制并提高免疫疗法的有效性.
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