{
  "abstract": "The combination immunotherapies, including those with atezolizumab and bevacizumab (Atez/Bev), have become standard therapy for hepatocellular carcinoma (HCC). However, its efficacy remains limited and reliable biomarkers are lacking. In this study, we analyzed paired tumor and background liver tissues from Atez/Bev-treated HCC patients and found that high programmed cell death-1 (PD-1) expression in CD8+ tumor-infiltrating lymphocytes (TILs) correlated with therapeutic response independent of etiology. RNA sequencing on the tumor samples revealed that the branched-chain amino acid (BCAA)-related metabolic pathway was enriched in the group with high PD-1 expression in CD8⁺ TILs. Along with in vitro experiments, we identified the importance of BCAAs for activation and differentiation of CD8+ T cells. In addition, BCAA metabolism was related to response to PD-1 blockade in not subcutaneous but intrahepatic mouse model–specific manner. Actually, public dataset analyses revealed that high expression of BCAT1, a key enzyme in BCAA metabolism, was associated with poor prognosis in HCC, but not in other cancer types. These findings suggest the importance of liver-specific BCAA metabolism in antitumor immunity and highlight the need to assess the tumor microenvironment within its organ-specific metabolic context.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Tumor Microenvironment, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan",
    "Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University, Okayama, Japan",
    "Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan",
    "Division of Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan",
    "Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan",
    "Division of Nutriomics and Oncology, RCAST, The University of Tokyo, Tokyo, Japan",
    "Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan",
    "Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan",
    "Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan",
    "Kindai University Faculty of Medicine, Osaka, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuma Fukumoto"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Fumiaki Mukohara",
      "orcid": "0009-0000-8866-0684"
    },
    {
      "affs": [
        0
      ],
      "name": "Momoko Iwatsuru"
    },
    {
      "affs": [
        0
      ],
      "name": "Youki Ueda",
      "orcid": "0000-0002-2627-8524"
    },
    {
      "affs": [
        2
      ],
      "name": "Hiroaki Kanzaki"
    },
    {
      "affs": [
        2
      ],
      "name": "Sadahisa Ogasawara"
    },
    {
      "affs": [
        3
      ],
      "name": "Jason Lin"
    },
    {
      "affs": [
        3
      ],
      "name": "Masahito Kawazu",
      "orcid": "0000-0003-4146-3629"
    },
    {
      "affs": [
        0
      ],
      "name": "Toshifumi Ninomiya"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Naoya Kemmotsu"
    },
    {
      "affs": [
        0
      ],
      "name": "Joji Nagasaki"
    },
    {
      "affs": [
        1
      ],
      "name": "Shinichi Toyooka"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "Tsuyoshi Osawa",
      "orcid": "0000-0002-9479-6665"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Takamasa Ishino",
      "orcid": "0000-0002-8601-0677"
    },
    {
      "affs": [
        0,
        2,
        8,
        9
      ],
      "name": "Yosuke Togashi",
      "orcid": "0000-0001-9910-0164"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/es1819178nyhf.bib",
  "cited_by": 0,
  "doi": "10.1038/s41388-026-04023-0",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723418/",
  "id": "es1819178nyhf",
  "issns": [
    "0950-9232",
    "1476-5594"
  ],
  "landing_url": "https://doi.org/10.1038/s41388-026-04023-0",
  "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",
      "Article"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
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  "openalex": "W7222788247",
  "pdf_url": "https://www.nature.com/articles/s41388-026-04023-0.pdf",
  "pmcid": "PMC13723418",
  "pmid": "42892653",
  "published": "2026-10-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/es1819178nyhf.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:03Z",
      "native_id": "PMC13723418",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41388-026-04023-0"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Liver-specific amino acid metabolism impacts on efficacy of cancer immunotherapy",
  "title_text": "Liver-specific amino acid metabolism impacts on efficacy of cancer immunotherapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:14Z",
  "url": "https://research.draconitic.com/paper/es1819178nyhf",
  "venue": "Oncogene",
  "versions": []
}