{
  "abstract": "Multi-drug resistance (MDR) is an almost inevitable endpoint of cancer therapy, driving rapid tumor progression, yet its evolutionary logic remains unclear because MDR tumors are rarely resected. Using paired therapy-naive and MDR melanoma specimens from a clinical trial, integrated with single-cell and spatial multi-omics and evaluated together with datasets from 10 additional cancer types, we identify a recurrent MDR-associated spatial nexus along the tumor-stroma interface. This niche juxtaposes CXCL14+ inflammatory cancer-associated fibroblasts (iCAFs), TREM2+ tumor-associated macrophages (TAMs), and AXL+ dedifferentiated tumor cells, and is accompanied by loss of tumor-reactive CXCL13+CD8+ T cells. In vitro, CXCL14 promotes macrophage migration and TREM2 induction, while TREM2+ TAMs suppress CXCL13+CD8+ T cells via CD86-CTLA4 signaling. TREM2+ TAMs also promote tumor dedifferentiation through oleic acid-driven GAS6-AXL activation. We develop an FAP/TREM2-targeting bispecific antibody to disrupt this spatial nexus and restore therapeutic sensitivity in MDR patient-derived xenograft models with favorable safety.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China",
    "Clinical Research Unit, Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai 200032, China",
    "Department of Radiation Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001, China",
    "Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China",
    "Department of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China",
    "Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China",
    "Department of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China",
    "Shanghai Cancer Institute, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China",
    "Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China",
    "Department of Plastic and Reconstructive Surgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian 361015, China",
    "Clinical Research Center for Precision Medicine of Abdominal Tumor of Fujian Province, Xiamen, Fujian 361015, China",
    "Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kangjie Shen"
    },
    {
      "affs": [
        1
      ],
      "name": "Lu Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zixu Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Junquan Song"
    },
    {
      "affs": [
        2
      ],
      "name": "Qiangcheng Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Minying Deng"
    },
    {
      "affs": [
        4
      ],
      "name": "Yingcheng Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Yang"
    },
    {
      "affs": [
        5
      ],
      "name": "Ming Ren"
    },
    {
      "affs": [
        6
      ],
      "name": "Shengbai Xue"
    },
    {
      "affs": [
        7
      ],
      "name": "Hongye Wang"
    },
    {
      "affs": [
        8
      ],
      "name": "Wenyu Song"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianyi Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chenlu Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiangying Xuan"
    },
    {
      "affs": [
        0
      ],
      "name": "Lilu Xie"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuan Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Qianrong Hu"
    },
    {
      "affs": [
        0,
        9,
        10
      ],
      "name": "Shaoluan Zheng"
    },
    {
      "affs": [
        3
      ],
      "name": "Rongkui Luo"
    },
    {
      "affs": [
        3
      ],
      "name": "Yingyong Hou"
    },
    {
      "affs": [
        11
      ],
      "name": "Yuhong Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Fazhi Qi"
    },
    {
      "affs": [
        4
      ],
      "name": "Jia Fan"
    },
    {
      "affs": [
        0
      ],
      "name": "Chuanyuan Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianying Gu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2cr21zdtcz4vr.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103052",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710381/",
  "id": "2cr21zdtcz4vr",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103052",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2403|Immune cells in cancer"
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  "openalex": "W7213432462",
  "pdf_url": null,
  "pmcid": "PMC13710381",
  "pmid": "42748914",
  "published": "2026-09-16",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/2cr21zdtcz4vr.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:21Z",
      "native_id": "PMC13710381",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103052"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
    }
  ],
  "title": "Single-cell and spatial multi-omics reveal a recurrent multicellular niche at the tumor-stroma interface in multidrug resistance",
  "title_text": "Single-cell and spatial multi-omics reveal a recurrent multicellular niche at the tumor-stroma interface in multidrug resistance",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:21Z",
  "url": "https://research.draconitic.com/paper/2cr21zdtcz4vr",
  "venue": "Cell Reports Medicine",
  "versions": []
}