{
  "abstract": "The dynamic reprogramming of the bone marrow (BM) microenvironment during metastatic progression is poorly defined. Through single-cell profiling of BM samples spanning benign conditions, high-risk bone metastatic potential localized prostate cancer (HMP) and established bone metastatic prostate cancer (PCa), we uncovered a primary tumor-to-BM signaling axis that orchestrates niche formation through neutrophil-mediated remodeling. Tumor-associated neutrophils (TANs) emerge during the HMP stage, persist throughout metastatic progression, correlate with poor patient prognosis, and exhibit direct immunosuppressive activity that contributes to a BM environment permissive to metastatic colonization. Functional and genetic studies showed that tumor-associated systemic IGF1 reprogrammed BM neutrophils through IGF1R-MAPK/ERK-KLF4 signaling, with IL-1{beta}, reactive oxygen species and nitric oxide contributing to TAN-mediated T cell suppression. Tumor-cell Igf1 perturbation, IGF1R blockade and neutrophil-specific Igf1r deletion attenuated TAN-associated BM remodeling, and reduced subsequent bone metastatic progression. In bone-metastasis models, combined IGF1R and PD-1 blockade suppressed bone-metastatic progression. Translationally, our investigator-initiated clinical trial (NCT06866548) of teprotumumab plus tislelizumab in patients with established metastatic castration-resistant prostate cancer (mCRPC) provided initial safety data and exploratory clinical observations. Together, these findings identify IGF1R-dependent neutrophil reprogramming as a functionally important component of the evolving PCa bone metastatic microenvironment and provide a rationale for therapeutic targeting of IGF1R signaling together with immune checkpoint blockade.",
  "abstract_shown": true,
  "affiliations": [
    "Shanghai Changzheng Hospital, Naval Medical University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "Y. Tang"
    },
    {
      "name": "X. Zhou"
    },
    {
      "name": "D. Li"
    },
    {
      "name": "Y. Liu"
    },
    {
      "name": "G. Zhu"
    },
    {
      "name": "J. Wang"
    },
    {
      "name": "X. Wu"
    },
    {
      "name": "D. Zhong"
    },
    {
      "name": "Z. Li"
    },
    {
      "name": "H. Huang"
    },
    {
      "name": "B.-Z. Qian"
    },
    {
      "name": "Y. Zhang"
    },
    {
      "name": "J. Xiao"
    },
    {
      "name": "Z. Yue"
    },
    {
      "name": "S. Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Ren"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7rphg4pg5g6g8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.08.757800",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757800v1.full",
  "id": "7rphg4pg5g6g8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757800v1",
  "language": null,
  "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": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2403|Immune cells in cancer"
    ]
  ],
  "openalex": "W7221070589",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757800v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7rphg4pg5g6g8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:52Z",
      "native_id": "10.64898/2026.10.08.757800",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757800v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Neutrophils orchestrate pre-metastatic immunosuppressive bone marrow remodeling during prostate cancer metastasis",
  "title_text": "Neutrophils orchestrate pre-metastatic immunosuppressive bone marrow remodeling during prostate cancer metastasis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:52Z",
  "url": "https://research.draconitic.com/paper/7rphg4pg5g6g8",
  "venue": "bioRxiv",
  "versions": []
}