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
Abstract
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.