{
  "abstract": "Background: Triple-negative breast cancer (TNBC) is characterized by limited therapeutic options and frequent immune escape, while the molecular mechanisms linking tumor-intrinsic programs with antitumor immunity remain incompletely understood.\n\nMethods: LARP1 was identified through integrative analysis of TNBC transcriptomic datasets and RNA-binding protein databases, and its broader clinical and prognostic relevance was evaluated in the METABRIC breast cancer cohort. Functional effects of LARP1 depletion or overexpression were evaluated in TNBC cells. Cell proliferation, apoptosis, CD73 expression, mRNA stability, and enrichment of NT5E mRNA in LARP1 immunoprecipitates were assessed. Activated human CD8+ T-cell co-culture, CD73 rescue experiments, and an immunocompetent 4T1 mouse model were used to evaluate immune regulation in vitro and in vivo .\n\nResults: LARP1 was elevated in breast cancer and TNBC-related expression comparisons. Exploratory analyses in the full TCGA-BRCA cohort suggested associations with survival and immune-cell composition, although LARP1 was not independently associated with overall survival after multivariable adjustment. In the independent METABRIC cohort, high LARP1 expression was associated with worse overall survival in both univariate and multivariable analyses (adjusted HR 1.422, 95% CI 1.215–1.664, P<0.001). LARP1 depletion suppressed TNBC-cell proliferation, promoted apoptosis, and enhanced CD8+ T-cell-mediated tumor-cell killing, whereas LARP1 overexpression increased proliferation and modestly reduced apoptosis. Mechanistically, LARP1 and NT5E expression showed a weak but statistically significant positive correlation in TCGA-BRCA, and LARP1 depletion reduced surface CD73 expression. CD73 mRNA was enriched in LARP1 immunoprecipitates and exhibited accelerated degradation following LARP1 loss, indicating that LARP1 maintains CD73 expression through mRNA stabilization. Restoration of CD73 attenuated the enhanced CD8+ T-cell activity induced by LARP1 depletion, including increased IFN-γ and granzyme B production and reduced PD-1 expression. In vivo , Larp1 silencing was associated with reduced 4T1 tumor growth, reduced Ki-67 and PCNA expression, increased CD8+ T-cell representation and proliferation within tumors, and decreased PD-1 expression on tumor-infiltrating CD8+ T cells.\n\nConclusions: LARP1 promotes TNBC progression by sustaining NT5E/CD73 expression and modulating tumor–T-cell interactions. In vivo , LARP1 depletion was associated with reduced tumor growth and altered intratumoral CD8+ T-cell profiles. These findings support further investigation of the LARP1–CD73 axis in TNBC.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Breast Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine",
    "Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xia Qiu"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiying Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yingxin Guan"
    },
    {
      "affs": [
        0
      ],
      "name": "Liping Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiahao Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Siyuan Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yibao Du"
    },
    {
      "affs": [
        0
      ],
      "name": "Yifan Gu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/evg5ehwtsf8x2.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1968375",
  "fulltext_url": null,
  "id": "evg5ehwtsf8x2",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1968375/full",
  "language": null,
  "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": [
    [
      "openalex",
      "1314|Adenosine and Purinergic Signaling"
    ]
  ],
  "openalex": "W7223182075",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1968375/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/evg5ehwtsf8x2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1968375",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1968375/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1314|Adenosine and Purinergic Signaling",
      "subfield": "physiology"
    }
  ],
  "title": "LARP1-mediated stabilization of CD73 mRNA promotes immune escape in triple-negative breast cancer",
  "title_text": "LARP1-mediated stabilization of CD73 mRNA promotes immune escape in triple-negative breast cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/evg5ehwtsf8x2",
  "venue": "Frontiers in Immunology",
  "versions": []
}