{
  "abstract": "Clear cell renal cell carcinoma (ccRCC) exhibits prominent immune infiltration and inflammatory signaling, yet the tumor-intrinsic mechanisms that promote immune evasion remain incompletely defined. CD276/B7-H3 is linked to an unfavorable prognosis in ccRCC, but its involvement in regulating inflammatory immune suppression requires clarification. This study aimed to determine whether tumor-cell CD276 drives nuclear factor kappa B (NF-κB)-interleukin (IL)-6-signal transducer and activator of transcription 3 (STAT3) signaling and macrophage-dependent immune evasion in ccRCC. The Cancer Genome Atlas (TCGA)-Kidney Renal Clear Cell Carcinoma cohort (KIRC) data were analyzed to assess CD276 expression, prognosis, and immune-related signatures. Stable CD276-knockdown 786-O and Caki-1 cells were generated using shRNA. Cell proliferation, invasion, NF-κB activation, cytokine secretion, and STAT3 signaling were evaluated using Cell Counting Kit-8 (CCK-8), Transwell assays, Western blotting, immunofluorescence, luciferase reporter assays, quantitative real-time polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA). Tumor-conditioned media were applied to THP-1-derived macrophages to examine STAT3-dependent polarization. Macrophage-T-cell co-culture assays were used to assess T-cell activation, cytokine secretion, and proliferation. CD276 was highly expressed in ccRCC tissues and was associated with poorer overall survival (OS) and enrichment of macrophage-related and IL-6-JAK-STAT3 immune signatures. CD276 knockdown inhibited ccRCC cell proliferation and invasion, reduced NF-κB p65 nuclear translocation and transcriptional activity, and decreased IL-6 production. CD276 silencing also attenuated STAT3 phosphorylation in tumor cells and macrophages. Conditioned media from CD276-knockdown cells suppressed CD206⁺CD163⁺ macrophage polarization, decreased ARG1 and IL10 expression, and increased iNOS expression. Functionally, macrophages exposed to CD276-deficient tumor media showed reduced suppression of CD3⁺ T-cell activation, interferon gamma (IFN-γ) and IL-2 secretion, and proliferation. Recombinant IL-6 restored macrophage-mediated T-cell suppression, whereas STAT3 inhibition or IL-6 neutralization reduced it. CD276 promotes ccRCC immune evasion by activating an NF-κB-IL-6-STAT3 signaling axis that drives immunosuppressive macrophage polarization and T-cell dysfunction.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China.",
    "Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Fan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingsuo Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chuanao Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jun Ouyang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhiyu Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6d03hjf4t2cce.bib",
  "cited_by": 0,
  "doi": "10.21037/tau-2026-0675",
  "fulltext_url": "https://europepmc.org/articles/PMC13741060",
  "id": "6d03hjf4t2cce",
  "issns": [
    "2223-4691"
  ],
  "landing_url": "https://europepmc.org/article/MED/42997165",
  "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": [
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7223947077",
  "pdf_url": "https://europepmc.org/articles/PMC13741060?pdf=render",
  "pmcid": "PMC13741060",
  "pmid": "42997165",
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6d03hjf4t2cce.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:41Z",
      "native_id": "MED:42997165",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42997165"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "CD276 promotes immune evasion in clear cell renal cell carcinoma via NF-κB-IL-6-STAT3 signaling crosstalk.",
  "title_text": "CD276 promotes immune evasion in clear cell renal cell carcinoma via NF-κB-IL-6-STAT3 signaling crosstalk.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:41Z",
  "url": "https://research.draconitic.com/paper/6d03hjf4t2cce",
  "venue": "Translational andrology and urology",
  "versions": []
}