{
  "abstract": "Elucidating how Epstein–Barr virus (EBV) shapes tumor–immune interactions is important for improving therapy in nasopharyngeal carcinoma (NPC). This multi‐cohort analysis integrates single‐cell, spatial, and bulk transcriptomic data with multiplex immunofluorescence and functional assays. Single‐cell profiling identifies stemness‐associated epithelial states and enrichment of SPP1+ tumor‐associated macrophages (TAMs) in EBV+ NPC. SPP1+ TAM abundance is associated with stemness‐associated epithelial features and dysfunctional T‐cell states, while high MIF and SPP1+ macrophage signatures are associated with shorter progression‐free survival. Within the EBV+ spatial cohort, SPP1+ TAMs co‐occur with stemness‐associated tumor cells, exhausted CD8+ T cells, and regulatory T cells in Niche 5, which is more frequent in non‐response tumors following chemoimmunotherapy. Functional experiments show increased MIF expression and secretion by EBV+ epithelial cells. MIF inhibition attenuates conditioned‐medium‐induced monocyte migration and SPP1‐associated TAM‐like programming, whereas recombinant MIF reproduces these effects. Conversely, macrophage‐derived SPP1 increases stemness‐associated marker expression and tumorsphere formation in EBV+ epithelial and tumor models. It also impairs primary CD8+ T‐cell proliferation, effector function, and cytotoxic activity while increasing exhaustion‐associated markers; CD44 blockade partially reverses these effects. Collectively, these findings support an EBV‐associated MIF–SPP1 macrophage–tumor/T‐cell crosstalk model linking stemness‐associated epithelial phenotypes with immune dysfunction and adverse clinical outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Nasopharyngeal Carcinoma Sun Yat‐sen University Cancer Center the State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangzhou China",
    "Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Department of Radiation Oncology Medical Research Center Sun Yat‐Sen Memorial Hospital Sun Yat‐Sen University Guangzhou China",
    "Department of Oncology The First Affiliated Hospital of Nanchang University Nanchang 330006 China",
    "Department of Radiation Oncology The First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease National Center for Respiratory Medicine Guangzhou Institute of Respiratory Health Guangzhou China",
    "Department of Medical Imaging Sun Yat‐sen University Cancer Center Guangzhou China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Guo‐Ying Liu",
      "orcid": "0000-0002-1053-7050"
    },
    {
      "affs": [
        0
      ],
      "name": "Shu‐Hui Lv",
      "orcid": "0000-0002-0980-8490"
    },
    {
      "affs": [
        0
      ],
      "name": "Shui‐Qing He",
      "orcid": "0000-0002-8873-0061"
    },
    {
      "affs": [
        2
      ],
      "name": "Yao‐Fei Jiang",
      "orcid": "0000-0001-9911-294X"
    },
    {
      "affs": [
        3
      ],
      "name": "Xing‐Si Peng"
    },
    {
      "affs": [
        3
      ],
      "name": "Jian‐Cong Sun"
    },
    {
      "affs": [
        3
      ],
      "name": "Fen He"
    },
    {
      "affs": [
        3
      ],
      "name": "Hai‐Yan Qin"
    },
    {
      "affs": [
        4
      ],
      "name": "Nian Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei‐Xin Bei",
      "orcid": "0009-0000-8726-3134"
    },
    {
      "affs": [
        3
      ],
      "name": "Lin‐Yu Zhao",
      "orcid": "0009-0002-2479-7280"
    },
    {
      "affs": [
        3
      ],
      "name": "Wan‐Qin Shen",
      "orcid": "0000-0002-6674-9482"
    },
    {
      "affs": [
        0
      ],
      "name": "Ze‐Yu Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan‐Qun Xiang"
    },
    {
      "affs": [
        3
      ],
      "name": "Wang‐Zhong Li",
      "orcid": "0000-0002-2744-8775"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cmj92t83bt2z2.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78450",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723717/",
  "id": "cmj92t83bt2z2",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.78450",
  "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 Article"
    ],
    [
      "openalex",
      "2403|Immune cells in cancer"
    ]
  ],
  "openalex": "W7225037390",
  "pdf_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.78450",
  "pmcid": "PMC13723717",
  "pmid": "42966886",
  "published": "2026-10-31",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/cmj92t83bt2z2.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:18Z",
      "native_id": "PMC13723717",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78450"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
    }
  ],
  "title": "Integrated Multiomic Analysis Reveals an EBV‐Associated MIF–SPP1+ Macrophage Axis Linking Tumor Stemness and Immune Dysfunction in Nasopharyngeal Carcinoma",
  "title_text": "Integrated Multiomic Analysis Reveals an EBV‐Associated MIF–SPP1+ Macrophage Axis Linking Tumor Stemness and Immune Dysfunction in Nasopharyngeal Carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:29Z",
  "url": "https://research.draconitic.com/paper/cmj92t83bt2z2",
  "venue": "Advanced Science",
  "versions": []
}