{
  "abstract": "Renal cell carcinoma (RCC) harbors an immunosuppressive tumor microenvironment that facilitates immune evasion and resistance to immune checkpoint blockade (ICB). However, the factors driving immune escape in RCC remain incompletely understood. In this study, transactivation response RNA-binding protein 2 (TARBP2) was identified as a critical regulator of the immune checkpoint molecule B7-H3. Elevated TARBP2 expression was associated with poor prognosis and ICB resistance in patients with RCC. Functionally, TARBP2 in RCC cells suppressed the intratumoral accumulation and cytotoxicity of T cells, particularly NK cells, thereby promoting immune escape. Mechanistically, nuclear TARBP2 interacted with p53-binding protein 1 (53BP1), inhibiting 53BP1 phase separation and subsequent p53 activation, thereby augmenting B7-H3 transcription. Furthermore, TARBP2 inhibition significantly enhanced ICB efficacy when combined with adoptive NK cell therapy. Collectively, these findings establish TARBP2 as a key mediator of immune evasion in RCC and a promising therapeutic target for overcoming ICB resistance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.",
    "Department of Urology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.",
    "Department of Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.",
    "Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.",
    "Department of Oncology and Southwest Cancer Center, Southwest Hospital of The Third Military Medical University (Army Medical University), Chongqing, China.",
    "Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, China.",
    "Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Disease, Changsha, China.",
    "Uro-Oncology Institute of Central South University, Changsha, China.",
    "Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, China.",
    "Department of Urology, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen, China.",
    "Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.",
    "Department of Urology and.",
    "State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.",
    "Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Minyu Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingjie Lin"
    },
    {
      "affs": [
        2
      ],
      "name": "Jiangquan Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Kezhi Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Guannan Shu"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhuting Tong"
    },
    {
      "affs": [
        4
      ],
      "name": "Mi Zhou"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "Liangmin Fu"
    },
    {
      "affs": [
        0
      ],
      "name": "Taowei Yang"
    },
    {
      "affs": [
        8
      ],
      "name": "Yihui Pan"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinwei Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinchen Luo"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "Wuyuan Liao"
    },
    {
      "affs": [
        0
      ],
      "name": "Qihao Li"
    },
    {
      "affs": [
        10
      ],
      "name": "Lican Liao"
    },
    {
      "affs": [
        0
      ],
      "name": "Hansen Lin"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Kangbo Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lizhen Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Chen"
    },
    {
      "affs": [
        0,
        13
      ],
      "name": "Junhang Luo"
    },
    {
      "affs": [
        10
      ],
      "name": "Jiaxing Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3jn5bptqka1d8.bib",
  "cited_by": 0,
  "doi": "10.1172/jci199525",
  "fulltext_url": "https://europepmc.org/articles/PMC13722402",
  "id": "3jn5bptqka1d8",
  "issns": [
    "0021-9738",
    "1558-8238"
  ],
  "landing_url": "https://europepmc.org/article/MED/42969235",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7225046417",
  "pdf_url": "https://europepmc.org/articles/PMC13722402?pdf=render",
  "pmcid": "PMC13722402",
  "pmid": "42969235",
  "published": "2026-11-02",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/3jn5bptqka1d8.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42969235",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42969235"
    },
    {
      "first_seen": "2026-11-04T12:22:00Z",
      "native_id": "PMC13722402",
      "source": "pmc",
      "url": "https://doi.org/10.1172/jci199525"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "TARBP2 facilitates renal cell carcinoma immune escape by suppressing 53BP1 phase separation to upregulate B7-H3.",
  "title_text": "TARBP2 facilitates renal cell carcinoma immune escape by suppressing 53BP1 phase separation to upregulate B7-H3.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:12Z",
  "url": "https://research.draconitic.com/paper/3jn5bptqka1d8",
  "venue": "The Journal of clinical investigation",
  "versions": []
}