{
  "abstract": "Tumors are embedded within complex microenvironments composed of malignant, immune and stromal cells, yet how coordinated cellular organization shapes tumor biology across cancers remains incompletely understood. Here we integrate single-cell transcriptomic profiles from over two million cells spanning 19 human epithelial cancers to construct a comprehensive pan-cancer atlas of tumor microenvironment (TME) organization. We identify cell subsets selectively enriched in tumors compared with normal tissues and show that their relative abundance is associated with clinical outcomes. By clustering tumors according to their cellular composition, we define eight recurrent cellular ecosystem subtypes that capture coordinated variation in immune and stromal architectures across cancer types. Comparative analyses reveal that these ecosystem states are associated with distinct tumor-intrinsic molecular programs, including differences in signaling pathway activity, transcriptional regulation and copy number alterations. We further uncover subtype-specific patterns of ligand-receptor interactions linking malignant cells with immune and stromal compartments and provide independent spatial support for these interactions using spatial transcriptomic data. Together, this work provides a unified framework for tumor ecosystem stratification and highlights cellular organization as a key dimension of tumor heterogeneity with potential implications for precision cancer therapy.",
  "abstract_shown": true,
  "affiliations": [
    "The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, The Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Inflammatory Biology, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.",
    "State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.",
    "Tianjin Institutes of Health Science, Tianjin, 301600, China.",
    "Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.",
    "State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.",
    "Department of Geriatrics, The Second Hospital of Tianjin Medical University, Tianjin Interdisciplinary Innovation Centre for Health and Meteorology, Tianjin, 300211, China. lixinsci@126.com.",
    "State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China. yuanjiapei@ihcams.ac.cn.",
    "Tianjin Institutes of Health Science, Tianjin, 301600, China. yuanjiapei@ihcams.ac.cn.",
    "The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, The Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Inflammatory Biology, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China. yy@tmu.edu.cn.",
    "Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China. yy@tmu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xiaoxiao Yang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yang Tong"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Yuting Wang"
    },
    {
      "affs": [
        4
      ],
      "name": "Peng Xie"
    },
    {
      "affs": [
        5
      ],
      "name": "Xin Li"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Jiapei Yuan"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Yang Yang",
      "orcid": "0000-0002-0273-9242"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/atv9hqvftjv58.bib",
  "cited_by": 0,
  "doi": "10.1186/s12943-026-02741-3",
  "fulltext_url": "https://europepmc.org/articles/PMC13688759",
  "id": "atv9hqvftjv58",
  "issns": [
    "1476-4598"
  ],
  "landing_url": "https://europepmc.org/article/MED/42907887",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
    ],
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7170929993",
  "pdf_url": "https://europepmc.org/articles/PMC13688759?pdf=render",
  "pmcid": "PMC13688759",
  "pmid": "42907887",
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/atv9hqvftjv58.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:59Z",
      "native_id": "MED:42907887",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42907887"
    },
    {
      "first_seen": "2026-10-30T13:45:50Z",
      "native_id": "d8e2713308934646b94fe04e62994c21",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s12943-026-02741-3"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Single-cell profiling defines cellular ecosystems and malignant cell state coupling across pan-cancer tumor microenvironments.",
  "title_text": "Single-cell profiling defines cellular ecosystems and malignant cell state coupling across pan-cancer tumor microenvironments.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:50Z",
  "url": "https://research.draconitic.com/paper/atv9hqvftjv58",
  "venue": "Molecular cancer",
  "versions": []
}