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^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

12 Scopus citations

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.

Original language	English
Article number	1046755
Pages (from-to)	918-927
Number of pages	10
Journal	Nature metabolism
Volume	7
Issue number	5
DOIs	https://doi.org/10.1038/s42255-025-01245-6
State	Published - 05 2025

Bibliographical note

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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. Article 1046755. https://doi.org/10.1038/s42255-025-01245-6

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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",

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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, vol. 7, no. 5, 1046755, pp. 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

Abstract

Bibliographical note

Keywords

UN SDGs

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