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

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

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

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^*

^*此作品的通信作者

研究成果: 期刊稿件 › 文章 › 同行評審

15 引文斯高帕斯（Scopus）

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.

原文	英語
文章編號	1046755
頁（從 - 到）	918-927
頁數	10
期刊	Nature metabolism
卷	7
發行號	5
DOIs	https://doi.org/10.1038/s42255-025-01245-6
出版狀態	已出版 - 05 2025

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10.1038/s42255-025-01245-6

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Chang, H. C., Tsai, C. Y., Hsu, C. L., Tai, T. S., Cheng, M. L., Chuang, Y. M., Tang, H. Y., Lin, K. J., Chen, J. J., Chang, S. H., Ko, Y. C., Chi, Y. W., Liu, H., Tan, B. C. M., Shen, C. R., Yang, C. W., Ho, P. C., & Yang, H. Y. (2025). Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations. Nature metabolism, 7(5), 918-927. 文章 1046755. https://doi.org/10.1038/s42255-025-01245-6

@article{08548a191e394b58874d61afdfbcbc79,

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

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.",

keywords = "Humans, Asparagine/deficiency, Asparaginase/therapeutic use, Reactive Oxygen Species/metabolism, Nasopharyngeal Carcinoma/drug therapy, CD8-Positive T-Lymphocytes/immunology, Signal Transduction/drug effects, T-Lymphocytes/immunology, Nasopharyngeal Neoplasms/drug therapy",

author = "Chang, \{Hsuan Chia\} and Tsai, \{Chung Ying\} and Hsu, \{Cheng Lung\} and Tai, \{Tzong Shyuan\} and Cheng, \{Mei Ling\} and Chuang, \{Yu Ming\} and Tang, \{Hsiang Yu\} and Lin, \{Kun Ju\} and Chen, \{Jia Jin\} and Chang, \{Szu Han\} and Ko, \{Yi Ching\} and Chi, \{Yu Wen\} and Hsuan Liu and Tan, \{Bertrand Chin Ming\} and Shen, \{Chia Rui\} and Yang, \{Chih Wei\} and Ho, \{Ping Chih\} and Yang, \{Huang Yu\}",

note = "{\textcopyright} 2025. The Author(s).",

year = "2025",

month = may,

doi = "10.1038/s42255-025-01245-6",

language = "英语",

volume = "7",

pages = "918--927",

journal = "Nature metabolism",

issn = "2522-5812",

publisher = "Nature Research",

number = "5",

}

Chang, HC, Tsai, CY, Hsu, CL, Tai, TS, Cheng, ML, Chuang, YM, Tang, HY, Lin, KJ, Chen, JJ, Chang, SH, Ko, YC, Chi, YW, Liu, H , Tan, BCM , Shen, CR , Yang, CW, Ho, PC & Yang, HY 2025, 'Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations', Nature metabolism, 卷 7, 編號 5, 1046755, 頁 918-927. https://doi.org/10.1038/s42255-025-01245-6

TY - JOUR

T1 - Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations

AU - Chang, Hsuan Chia

AU - Tsai, Chung Ying

AU - Hsu, Cheng Lung

AU - Tai, Tzong Shyuan

AU - Cheng, Mei Ling

AU - Chuang, Yu Ming

AU - Tang, Hsiang Yu

AU - Lin, Kun Ju

AU - Chen, Jia Jin

AU - Chang, Szu Han

AU - Ko, Yi Ching

AU - Chi, Yu Wen

AU - Liu, Hsuan

AU - Tan, Bertrand Chin Ming

AU - Shen, Chia Rui

AU - Yang, Chih Wei

AU - Ho, Ping Chih

AU - Yang, Huang Yu

PY - 2025/5

Y1 - 2025/5

N2 - 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.

AB - 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.

KW - Humans

KW - Asparagine/deficiency

KW - Asparaginase/therapeutic use

KW - Reactive Oxygen Species/metabolism

KW - Nasopharyngeal Carcinoma/drug therapy

KW - CD8-Positive T-Lymphocytes/immunology

KW - Signal Transduction/drug effects

KW - T-Lymphocytes/immunology

KW - Nasopharyngeal Neoplasms/drug therapy

UR - https://www.scopus.com/pages/publications/86000334026

U2 - 10.1038/s42255-025-01245-6

DO - 10.1038/s42255-025-01245-6

M3 - 文章

C2 - 40045118

AN - SCOPUS:86000334026

SN - 2522-5812

VL - 7

SP - 918

EP - 927

JO - Nature metabolism

JF - Nature metabolism

IS - 5

M1 - 1046755

ER -

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

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