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<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>

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Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月5日

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  • 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

摘要

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.