Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations
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<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.
Authors
- Sanders Chang (ORCID: https://orcid.org/0000-0003-3543-0310)
- Yi-Ching Ko
- Kun-Ju Lin
- Ping‐Chih Ho (ORCID: https://orcid.org/0000-0003-3078-3774)
- Hsuan Liu (ORCID: https://orcid.org/0000-0003-4691-2518)
- Hsiang-Yu Tang (ORCID: https://orcid.org/0000-0002-2536-6370)
- Tzong-Shyuan Tai (ORCID: https://orcid.org/0000-0003-0575-914X)
- Yu-Wen Chi
- Huang‐Yu Yang (ORCID: https://orcid.org/0000-0001-6826-9717)
- Bertrand Chin‐Ming Tan (ORCID: https://orcid.org/0000-0002-2218-7115)
- Chia‐Rui Shen (ORCID: https://orcid.org/0000-0002-8386-3965)
- Chung‐Ying Tsai (ORCID: https://orcid.org/0000-0002-1444-5647)
- Chih‐Wei Yang (ORCID: https://orcid.org/0000-0001-9782-9517)
- Jia-Jin Chen
- Cheng-Lung Hsu
- Hsuan-Chia Chang
- Yu‐Ming Chuang
- Mei‐Ling Cheng
Institutions
- Johns Hopkins University (US)
- Chang Gung University (TW)
- Chang Gung Memorial Hospital (TW)
- Linkou Chang Gung Memorial Hospital (TW)
- Ludwig Cancer Research (CH)
- University of Lausanne (CH)
Publication Details
- Journal
- Nature Metabolism
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1038/s42255-025-01245-6
- Citations
- 28
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 26.21
Funders
- National Science Foundation
- Cancer Research Institute
- Ludwig Institute for Cancer Research
- Chang Gung Memorial Hospital
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Chang Gung University
- Shanghai Educational Development Foundation
- Chang Gung Medical Foundation
- Université de Lausanne
- Helmut Horten Stiftung