{
  "abstract": "Numerous solid tumours have bone as one of their most common sites of distant metastasis, and bone metastasis causes skeletal-related events (SREs) that impair quality of life and portend poor prognosis. Bone metastasis arises not from invasive tumour cells alone but through mutual adaptation and co-evolution between tumour cells and the bone microenvironment. A key mechanism of immune evasion is the establishment of an immunosuppressive microenvironment, wherein tumour-derived cytokines, metabolic reprogramming, and extracellular vesicles drive M2 macrophage polarization, CD8+ T-cell exhaustion, regulatory T-cell enrichment, and natural killer cell dysfunction. Transforming growth factor-β (TGF-β) released during the “tumour-bone” vicious cycle further amplifies local immunosuppression, and metabolic reprogramming depletes glucose and amino acids while accumulating lactate, directly impairing effector T-cell function. Immune checkpoint inhibitor (ICI) therapy shows limited efficacy in bone metastases; however, combination strategies including bone-protective agents (denosumab, bisphosphonates), metabolic modulators, cytokine- or extracellular vesicle-targeted agents, novel nanodelivery systems, and engineered cell therapies demonstrate encouraging preclinical and early clinical promise for reversing immunosuppression. Translation still faces major challenges, including microenvironmental heterogeneity, a lack of bone-specific biomarkers, combination-related toxicity, and delivery bottlenecks. This review aims to synthesize the mechanisms underlying the immunosuppressive bone-metastasis microenvironment and to appraise current and emerging combination strategies, thereby informing individualized treatment for patients with bone metastases.",
  "abstract_shown": true,
  "affiliations": [
    "Affiliated School of Pediatrics, Nanjing Medical University, Nanjing, China",
    "Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China",
    "Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, UK",
    "College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Minghao Ba"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuzhu Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Peng Jiang"
    },
    {
      "affs": [
        2
      ],
      "name": "Shanshan Cai"
    },
    {
      "affs": [
        3
      ],
      "name": "Xin Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Tongmei Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6k5m01jtjg6wc.bib",
  "cited_by": 0,
  "doi": "10.32604/or.2026.090531",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732345/",
  "id": "6k5m01jtjg6wc",
  "issns": [
    "0965-0407",
    "1555-3906"
  ],
  "landing_url": "https://doi.org/10.32604/or.2026.090531",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2730|Bone health and treatments"
    ]
  ],
  "openalex": "W7223414236",
  "pdf_url": "https://www.techscience.com/or/online/detail/28758/TSP_OR_90531.pdf",
  "pmcid": "PMC13732345",
  "pmid": "42985499",
  "published": "2026-10-28",
  "publisher": "Tech Science Press",
  "ris": "https://research.draconitic.com/paper/6k5m01jtjg6wc.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:21Z",
      "native_id": "PMC13732345",
      "source": "pmc",
      "url": "https://doi.org/10.32604/or.2026.090531"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Bone health and treatments",
      "subfield": "oncology"
    }
  ],
  "title": "Bone Metastasis and the Immunosuppressive Tumor Microenvironment: Mechanisms and Therapeutic Strategies",
  "title_text": "Bone Metastasis and the Immunosuppressive Tumor Microenvironment: Mechanisms and Therapeutic Strategies",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:21Z",
  "url": "https://research.draconitic.com/paper/6k5m01jtjg6wc",
  "venue": "Oncology Research",
  "versions": []
}