{
  "abstract": "The development of effective antibody therapeutics has been hampered by a lack of methods to measure drug delivery and activity within tumors at single-cell resolution. Here we introduce single-cell spatial pharmacobiology (SSP), an experimental and analytical framework that integrates in situ imaging of a systemically infused, fluorescently labeled therapeutic antibody with high-plex spatial proteomics to quantify antibody distribution, target engagement and tumor microenvironment (TME) architecture. We applied SSP to tumor tissues from participants with head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma who received the antibody panitumumab-IRDye800 in phase 1 trials. SSP identified pronounced spatial heterogeneity in single-cell drug delivery and target engagement, shaped by conserved stromal barriers, including periostin-rich extracellular matrix assemblies and fibroblast-activation-protein-positive cancer-associated fibroblast neighborhoods, which were associated with reduced antibody delivery in both tumor types. SSP measures drug-target-TME interactions in human tumors and can support studies of resistance mechanisms, dosing strategies and discovery of spatial biomarkers for precision oncology.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA. guolanlu@stanford.edu",
    "Department of Urology, Stanford University School of Medicine, Stanford, CA, USA. guolanlu@stanford.edu",
    "Department of Biomedical Engineering, Duke University, Durham, NC, USA",
    "Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA",
    "Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA",
    "Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany",
    "Department of Surgery, Stanford University, Stanford, CA, USA",
    "Department of Urology, Stanford University School of Medicine, Stanford, CA, USA",
    "Department of Otolaryngology, Tulane University School of Medicine, New Orleans, LA, USA",
    "Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN, USA",
    "Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA",
    "Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, Germany",
    "Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany",
    "Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA",
    "Institute for Bioengineering of Catalonia, Barcelona Institute of Science and Technology, Barcelona, Spain",
    "Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA",
    "Department of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA, USA",
    "Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA",
    "Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA",
    "Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA",
    "Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA. gnolan@stanford.edu",
    "Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. gnolan@stanford.edu",
    "Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA. e.rosenthal@vumc.org",
    "Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN, USA. e.rosenthal@vumc.org"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Guolan Lu",
      "orcid": "0000-0002-5023-3465"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "John W. Hickey",
      "orcid": "0000-0001-9961-7673"
    },
    {
      "affs": [
        5,
        3,
        4
      ],
      "name": "Maximilian Haist",
      "orcid": "0000-0002-6720-7570"
    },
    {
      "affs": [
        6
      ],
      "name": "Xulei Qin"
    },
    {
      "affs": [
        7
      ],
      "name": "Dr. Emily Zhao"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Abdullah Naveed"
    },
    {
      "affs": [
        10,
        4
      ],
      "name": "Erna Forgó",
      "orcid": "0000-0001-6320-0905"
    },
    {
      "affs": [
        11,
        12,
        3
      ],
      "name": "Marc‐Andrea Baertsch",
      "orcid": "0000-0002-4000-6904"
    },
    {
      "affs": [
        13,
        9
      ],
      "name": "Lucas Mani",
      "orcid": "0009-0002-8638-4705"
    },
    {
      "affs": [
        3,
        4,
        14
      ],
      "name": "Xavier Rovira Clavé",
      "orcid": "0000-0001-9994-7007"
    },
    {
      "affs": [
        13
      ],
      "name": "Andrey Finegersh",
      "orcid": "0000-0002-2639-2132"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Yury Goltsev",
      "orcid": "0000-0003-4079-7969"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Chiara Caraccio",
      "orcid": "0000-0002-3580-1348"
    },
    {
      "affs": [
        13
      ],
      "name": "Nynke S. van den Berg",
      "orcid": "0000-0002-3315-2647"
    },
    {
      "affs": [
        13,
        9
      ],
      "name": "Marisa E. Hom",
      "orcid": "0000-0003-1319-5110"
    },
    {
      "affs": [
        4
      ],
      "name": "Deana R.C. Colburg",
      "orcid": "0000-0002-8287-9455"
    },
    {
      "affs": [
        4
      ],
      "name": "Brock A. Martin",
      "orcid": "0000-0001-8539-9556"
    },
    {
      "affs": [
        4
      ],
      "name": "Christina S. Kong",
      "orcid": "0000-0003-2098-6842"
    },
    {
      "affs": [
        15
      ],
      "name": "Natalie S. Lui",
      "orcid": "0000-0002-6602-6372"
    },
    {
      "affs": [
        16
      ],
      "name": "George Albert Fisher",
      "orcid": "0000-0002-6828-3938"
    },
    {
      "affs": [
        16
      ],
      "name": "Alexander Dimitrios Colevas",
      "orcid": "0000-0003-3849-4264"
    },
    {
      "affs": [
        4
      ],
      "name": "Robert B. West",
      "orcid": "0000-0002-8330-8283"
    },
    {
      "affs": [
        17,
        18,
        19
      ],
      "name": "Greg M. Thurber",
      "orcid": "0000-0001-7570-2080"
    },
    {
      "affs": [
        6
      ],
      "name": "George A. Poultsides",
      "orcid": "0000-0002-7584-0405"
    },
    {
      "affs": [
        20,
        21
      ],
      "name": "Garry P. Nolan",
      "orcid": "0000-0002-8862-9043"
    },
    {
      "affs": [
        22,
        23
      ],
      "name": "Eben Lloyd Rosenthal",
      "orcid": "0000-0003-0294-5203"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4qbvej3y46eqg.bib",
  "cited_by": 17,
  "doi": "10.1038/s41587-026-03152-x",
  "fulltext_url": null,
  "id": "4qbvej3y46eqg",
  "issns": [
    "0733-222X",
    "1087-0156",
    "1546-1696",
    "2331-3684"
  ],
  "landing_url": "https://doi.org/10.1038/s41587-026-03152-x",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "2403|Monoclonal and Polyclonal Antibodies Research"
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  "openalex": "W7163382970",
  "pdf_url": null,
  "pmcid": "PMC13390730",
  "pmid": "42236958",
  "published": "2026-06-03",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/4qbvej3y46eqg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:54Z",
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      "url": "https://doi.org/10.1038/s41587-026-03152-x"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Monoclonal and Polyclonal Antibodies Research",
      "subfield": "immunology"
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    {
      "field": "medicine",
      "origin": "openalex:2741|Monoclonal and Polyclonal Antibodies Research",
      "subfield": "imaging"
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  ],
  "title": "Single-cell spatial pharmacobiology identifies conserved stromal barriers to therapeutic antibody delivery in human solid tumors",
  "title_text": "Single-cell spatial pharmacobiology identifies conserved stromal barriers to therapeutic antibody delivery in human solid tumors",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:11Z",
  "url": "https://research.draconitic.com/paper/4qbvej3y46eqg",
  "venue": "Nature Biotechnology",
  "versions": []
}