{
  "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.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00262-026-04503-y.",
  "abstract_shown": true,
  "affiliations": [
    "Department 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",
    "Department of General Practice, Shenzhen Hospital of Southern Medical University, Shenzhen, 518100 China",
    "Experimental Animal Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 China",
    "Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510220 China",
    "Translational and Clinical Research Institute, FMS, Newcastle University, Newcastle Upon Tyne, NE4 4HH UK"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhiming Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Siwei Li"
    },
    {
      "name": "Mengjie Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Li Gong"
    },
    {
      "name": "Xinyu Lu"
    },
    {
      "affs": [
        3
      ],
      "name": "Weikang Xu"
    },
    {
      "name": "An-an Chen"
    },
    {
      "name": "Yiyue Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Changsheng He"
    },
    {
      "name": "Guoheng Mo"
    },
    {
      "name": "Yuting Xie"
    },
    {
      "name": "Si-an Yue"
    },
    {
      "affs": [
        4
      ],
      "name": "Lei Huang"
    },
    {
      "name": "Chou Yang"
    },
    {
      "name": "Jinlin Hou"
    },
    {
      "name": "Wei Zhu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6skcaxx8310wt.bib",
  "cited_by": 0,
  "doi": "10.1007/s00262-026-04503-y",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731632/",
  "id": "6skcaxx8310wt",
  "issns": [
    "0340-7004",
    "1432-0851"
  ],
  "landing_url": "https://doi.org/10.1007/s00262-026-04503-y",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "1307|Aldose Reductase and Taurine"
    ]
  ],
  "openalex": "W7196948209",
  "pdf_url": null,
  "pmcid": "PMC13731632",
  "pmid": "42975718",
  "published": "2026-08-06",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/6skcaxx8310wt.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:47Z",
      "native_id": "PMC13731632",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00262-026-04503-y"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Aldose Reductase and Taurine",
      "subfield": "cell-biology"
    }
  ],
  "title": "Taurine bolsters adoptive T cell therapy efficacy against hepatocellular carcinoma by reprogramming T cell function",
  "title_text": "Taurine bolsters adoptive T cell therapy efficacy against hepatocellular carcinoma by reprogramming T cell function",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:47Z",
  "url": "https://research.draconitic.com/paper/6skcaxx8310wt",
  "venue": "Cancer Immunology, Immunotherapy : CII",
  "versions": []
}