{"title":"Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations","authors":"Hsuan-Chia Chang, Chung-Ying Tsai, Cheng-Lung Hsu, Tzong-Shyuan Tai, Mei-Ling Cheng, Yu-Ming Chuang, Hsiang-Yu Tang, Kun-Ju Lin, Jia-Jin Chen, Szu-Han Chang, Yi-Ching Ko, Yu-Wen Chi, Hsuan Liu, Bertrand Chin-Ming Tan, Chia-Rui Shen, Chih-Wei Yang, Ping-Chih Ho, Huang-Yu Yang","doi":"10.1038/s42255-025-01245-6","DOIUrl":null,"url":null,"abstract":"<p>Preclinical studies have shown that asparagine deprivation enhances T cell antitumour responses. Here we apply compassionate use of <span>l</span>-asparaginase, usually employed to treat blood malignancies, on patients with recurrent metastatic nasopharyngeal carcinoma. The use of <span>l</span>-asparaginase notably enhances immune-checkpoint blockade therapy in patients by strengthening CD8<sup>+</sup>T cell fitness. Our study shows that this combination is a promising avenue for clinical application and provides further mechanistic insight into how asparagine restriction rewires T cell metabolism.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"35 1","pages":""},"PeriodicalIF":18.9000,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s42255-025-01245-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Preclinical studies have shown that asparagine deprivation enhances T cell antitumour responses. Here we apply compassionate use of l-asparaginase, usually employed to treat blood malignancies, on patients with recurrent metastatic nasopharyngeal carcinoma. The use of l-asparaginase notably enhances immune-checkpoint blockade therapy in patients by strengthening CD8+T cell fitness. Our study shows that this combination is a promising avenue for clinical application and provides further mechanistic insight into how asparagine restriction rewires T cell metabolism.
临床前研究表明，剥夺天冬酰胺可增强 T 细胞的抗肿瘤反应。在这里，我们将通常用于治疗血液恶性肿瘤的天冬酰胺酶用于复发性转移性鼻咽癌患者。通过加强 CD8+T 细胞的适应性，l-天冬酰胺酶的使用显著增强了患者的免疫检查点阻断疗法。我们的研究表明，这种组合是一种很有前景的临床应用途径，并进一步从机理上揭示了天冬酰胺限制如何重塑 T 细胞代谢。
期刊介绍：
Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.
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