Taurine bolsters adoptive T cell therapy efficacy against hepatocellular carcinoma by reprogramming T cell function
5 affiliations
- 1Department of Gastroenterology, Integrative Microecology Clinical Center, Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Hospital, Southern Medical University, Shenzhen, 518101 China
- 2Department of General Practice, Shenzhen Hospital of Southern Medical University, Shenzhen, 518100 China
- 3Experimental Animal Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 China
- 4Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510220 China
- 5Translational and Clinical Research Institute, FMS, Newcastle University, Newcastle Upon Tyne, NE4 4HH UK
Abstract
Adoptive T cell therapy for advanced hepatocellular carcinoma (HCC) is limited by the immunosuppressive tumor microenvironment, which impairs T-cell function. Overcoming this immunosuppression and restoring T-cell functionality are crucial for improving therapeutic efficacy. Here, we investigated the role of taurine in regulating alpha-fetoprotein (AFP)-specific T-cell receptor-engineered T cells (TCR-T) function. Metabolomic profiling revealed that intracellular taurine levels declined during the early phase of T-cell activation, while expression of the taurine transporter SLC6A6 increased over time. In addition, taurine abundance was lower in HCC tissues than in normal liver tissues in vivo, suggesting that taurine availability is reduced during both T-cell activation and tumor progression. Functionally, taurine supplementation enhanced the cytotoxic activity, persistence, and intratumoral infiltration of AFP-specific TCR-T, while reducing exhaustion and apoptosis after repetitive tumor stimulation. In contrast, taurine-limited conditions impaired T-cell proliferation and survival, attenuated antitumor activity in vitro and in vivo, and promoted an exhaustion-prone phenotype. Taurine supplementation also partially restored the function of β-alanine-preconditioned T cells. Mechanistically, transcriptomic and proteomic analyses identified PI3K-AKT signaling as a key pathway associated with taurine-mediated T-cell regulation. Taurine-limited T cells showed reduced AKT phosphorylation and developed a metabolically stressed state characterized by increased mitochondrial respiration, glycolytic activity, reactive oxygen species production and mitochondrial structural abnormalities during activation. Together, these findings identify taurine availability as an important metabolic regulator of engineered T-cell fitness and support taurine-based metabolic conditioning as a potential strategy to improve TCR-T therapy for HCC.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00262-026-04503-y.
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BibTeX
@article{zhang2026taurine,
title = {{Taurine bolsters adoptive T cell therapy efficacy against hepatocellular carcinoma by reprogramming T cell function}},
author = {Zhiming Zhang and Siwei Li and Mengjie Li and Li Gong and Xinyu Lu and Weikang Xu and An-an Chen and Yiyue Wang and Changsheng He and Guoheng Mo and Yuting Xie and Si-an Yue and Lei Huang and Chou Yang and Jinlin Hou and Wei Zhu},
journal = {Cancer Immunology, Immunotherapy : CII},
year = {2026},
month = aug,
doi = {10.1007/s00262-026-04503-y},
url = {https://doi.org/10.1007/s00262-026-04503-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Taurine bolsters adoptive T cell therapy efficacy against hepatocellular carcinoma by reprogramming T cell function
AU - Zhiming Zhang
AU - Siwei Li
AU - Mengjie Li
AU - Li Gong
AU - Xinyu Lu
AU - Weikang Xu
AU - An-an Chen
AU - Yiyue Wang
AU - Changsheng He
AU - Guoheng Mo
AU - Yuting Xie
AU - Si-an Yue
AU - Lei Huang
AU - Chou Yang
AU - Jinlin Hou
AU - Wei Zhu
PY - 2026
DA - 2026/08/06
JO - Cancer Immunology, Immunotherapy : CII
DO - 10.1007/s00262-026-04503-y
UR - https://doi.org/10.1007/s00262-026-04503-y
AB - Adoptive T cell therapy for advanced hepatocellular carcinoma (HCC) is limited by the immunosuppressive tumor microenvironment, which impairs T-cell function. Overcoming this immunosuppression and restoring T-cell functionality are crucial for improving therapeutic efficacy. Here, we investigated the role of taurine in regulating alpha-fetoprotein (AFP)-specific T-cell receptor-engineered T cells (TCR-T) function. Metabolomic profiling revealed that intracellular taurine levels declined during the early phase of T-cell activation, while expression of the taurine transporter SLC6A6 increased over time. In addition, taurine abundance was lower in HCC tissues than in normal liver tissues in vivo, suggesting that taurine availability is reduced during both T-cell activation and tumor progression. Functionally, taurine supplementation enhanced the cytotoxic activity, persistence, and intratumoral infiltration of AFP-specific TCR-T, while reducing exhaustion and apoptosis after repetitive tumor stimulation. In contrast, taurine-limited conditions impaired T-cell proliferation and survival, attenuated antitumor activity in vitro and in vivo, and promoted an exhaustion-prone phenotype. Taurine supplementation also partially restored the function of β-alanine-preconditioned T cells. Mechanistically, transcriptomic and proteomic analyses identified PI3K-AKT signaling as a key pathway associated with taurine-mediated T-cell regulation. Taurine-limited T cells showed reduced AKT phosphorylation and developed a metabolically stressed state characterized by increased mitochondrial respiration, glycolytic activity, reactive oxygen species production and mitochondrial structural abnormalities during activation. Together, these findings identify taurine availability as an important metabolic regulator of engineered T-cell fitness and support taurine-based metabolic conditioning as a potential strategy to improve TCR-T therapy for HCC. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00262-026-04503-y.
SN - 0340-7004
SN - 1432-0851
ER -