{
  "abstract": "Prostate cancer frequently metastasizes to bone, marking incurable disease. This progression is driven by an immunologically cold bone tumor microenvironment that fosters resistance to therapy. To define the mechanisms underlying this uniquely immunosuppressive niche, we applied spatial single-cell analyses across primary tumors and metastatic sites. Bone metastases showed marked suppression of tumor-intrinsic type I interferon (IFN-I) signaling and loss of antigen presentation, features that were strongly associated with reduced bone metastasis-free survival. Tumor-intrinsic IFN-I expression correlated with memory T-cell infiltration, whereas the bone myeloid compartment was enriched for protumor macrophages and showed reduced dendritic cell activation and antigen presentation. Digital spatial profiling of matched tumors revealed a broad loss of IFN-I-regulated immunostimulatory and checkpoint molecules. Notably, B7-H3, a putative negative regulator of IFN-I, was highly expressed in bone metastases and inversely associated with antigen presentation. These findings define bone-specific mechanisms of immune resistance and highlight therapeutic vulnerabilities that could inform precision therapeutic strategies for prostate cancer.\n\nSignificance:: Prostate cancer bone metastases establish a tumor-driven, immunosuppressive niche featuring global impairment of IFN-I signaling and antigen presentation coupled to elevated B7-H3, highlighting clinically actionable vulnerabilities in advanced prostate cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Cancer Evolution and Metastasis Program, Peter MacCallum Cancer Centre, Melbourne, Australia.",
    "Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.",
    "Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Australia.",
    "Department of Molecular and Translational Science, Monash University, Clayton, Australia.",
    "Immunobiology of Inflammation Group, German Rheumatology Research Center (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.",
    "Prostate Cancer Research Group, Cancer Program, Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Australia.",
    "St.Vincent’s Institute of Medical Research, Fitzroy, Australia.",
    "Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Australia.",
    "Department of Urology, Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.",
    "Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.",
    "Collaborative Centre for Cancer Genomic Medicine, Victorian Comprehensive Cancer Centre, University of Melbourne, Parkville, Australia.",
    "Department of Urology, Frankston Hospital, Frankston, Australia.",
    "Prostate Cancer Research Group, Cancer Program, Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Australia.",
    "Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.",
    "Department of Medical Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Katie L. Owen",
      "orcid": "0000-0002-9580-214X"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Linden J. Gearing",
      "orcid": "0000-0003-3508-3056"
    },
    {
      "affs": [
        5
      ],
      "name": "Birunthi Niranjan",
      "orcid": "0000-0002-9555-8378"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Madawa Jayawardana",
      "orcid": "0000-0002-6990-1785"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Thomas B. Chadwick",
      "orcid": "0009-0003-1653-7582"
    },
    {
      "affs": [
        0
      ],
      "name": "Holly I. Newman",
      "orcid": "0009-0002-8326-621X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sirui Weng",
      "orcid": "0000-0002-9130-8689"
    },
    {
      "affs": [
        0,
        1,
        6,
        7
      ],
      "name": "Anna S. Trigos",
      "orcid": "0000-0002-5915-2952"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lisa M. Devereux",
      "orcid": "0000-0003-2435-5888"
    },
    {
      "affs": [
        8,
        9,
        10
      ],
      "name": "Bethany K. Campbell",
      "orcid": "0000-0001-6859-8158"
    },
    {
      "affs": [
        0
      ],
      "name": "Anupama Pasam",
      "orcid": "0000-0003-1577-9208"
    },
    {
      "affs": [
        8,
        9,
        10,
        11
      ],
      "name": "Niall M. Corcoran",
      "orcid": "0000-0003-4483-6945"
    },
    {
      "affs": [
        1,
        12,
        13
      ],
      "name": "Renea A. Taylor",
      "orcid": "0000-0003-2609-2380"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Christopher M. Hovens",
      "orcid": "0000-0002-0610-1289"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Paul J. Hertzog",
      "orcid": "0000-0002-1373-8472"
    },
    {
      "affs": [
        1,
        14
      ],
      "name": "Shahneen Sandhu",
      "orcid": "0000-0002-8660-4475"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nicole M. Haynes",
      "orcid": "0000-0003-4991-6274"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Belinda S. Parker",
      "orcid": "0000-0002-8333-1926"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ewjr72pksazwk.bib",
  "cited_by": 0,
  "doi": "10.1158/0008-5472.can-26-2386",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13728789/",
  "id": "ewjr72pksazwk",
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    "1538-7445"
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  "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",
      "Biomarkers"
    ],
    [
      "heading",
      "Cancer Landscapes"
    ],
    [
      "heading",
      "Checkpoint Blockade"
    ],
    [
      "heading",
      "Immune Cells and the Microenvironment"
    ],
    [
      "heading",
      "Immunotherapy"
    ],
    [
      "heading",
      "Metastasis"
    ],
    [
      "heading",
      "Metastasis Biomarkers"
    ],
    [
      "heading",
      "Progression, Invasion & Metastasis"
    ],
    [
      "heading",
      "Tumor Microenvironment"
    ],
    [
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      "2730|Cancer Immunotherapy and Biomarkers"
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  "openalex": "W7202182644",
  "pdf_url": null,
  "pmcid": "PMC13728789",
  "pmid": "42578821",
  "published": "2026-08-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ewjr72pksazwk.ris",
  "sources": [
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      "first_seen": "2026-11-07T12:21:42Z",
      "native_id": "PMC13728789",
      "source": "pmc",
      "url": "https://doi.org/10.1158/0008-5472.can-26-2386"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Spatial Profiling Reveals Immune Escape Pathways and Therapeutic Vulnerabilities in Prostate Cancer Bone Metastases",
  "title_text": "Spatial Profiling Reveals Immune Escape Pathways and Therapeutic Vulnerabilities in Prostate Cancer Bone Metastases",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:42Z",
  "url": "https://research.draconitic.com/paper/ewjr72pksazwk",
  "venue": "Cancer Research",
  "versions": []
}