{
  "abstract": "CD73 is an emerging immunotherapy target that is overexpressed in many tumors and generates an adenosine-rich microenvironment to suppress antitumor immunity. In low-grade endometrial carcinoma, CD73 expression varies, and its impact on tumor immunobiology is unknown. Using two microsatellite-stable, grade 2 endometrioid endometrial carcinoma cohorts, in vitro NT5E (CD73) knockout/knockdown, and single-cell and spatial analyses, we show that cancer cell CD73 loss promotes a dual inflammatory and immunosuppressive microenvironment. Cancer cell CD73 loss was associated with increased lymphovascular space invasion and worse recurrence-free and overall survival, whereas stromal CD73 expression did not correlate with outcomes. CD73 downregulation induced pro-inflammatory gene expression, which strongly correlated with upregulation of immunosuppressive genes, including CD274 (PD-L1), suggesting a compensatory mechanism limiting antitumor immunity. Tumors with low cancer cell CD73 exhibited higher PD-L1 expression that correlated with increased CD3+ T-cell infiltration, reflecting an immune-engaged but checkpoint-restrained microenvironment. Single-cell analyses demonstrated that NT5E+ nonimmune cells in immune-responsive clusters were three times less likely to express CD274. In clinically relevant low-grade endometrial carcinoma models, functional studies confirmed that CD73 loss promoted both pro-inflammatory and immunosuppressive programs. These results reveal a context-specific role for CD73 in shaping the immune landscape of low-grade endometrial carcinoma that is distinct from its function in other solid tumors.\n\nSignificance:: Unlike most cancers, in which CD73 drives immunosuppression via overexpression, we show that cancer cell CD73 loss promotes an inflammatory yet compensatory immunosuppressive microenvironment in low-grade endometrial carcinoma, revealing a context-specific role. CD73 loss in endometrial carcinoma therefore may be as immunologically significant as its overexpression in other cancers.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.",
    "Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.",
    "Graduate Curriculum in Pathobiology and Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.",
    "Department of Internal Medicine, University of Texas McGovern Medical School, Houston, Texas.",
    "Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.",
    "Department of Biomedical Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.",
    "UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hannah N. Lee",
      "orcid": "0009-0001-1884-9032"
    },
    {
      "affs": [
        0
      ],
      "name": "Xingyuan Zhang",
      "orcid": "0009-0009-9072-948X"
    },
    {
      "affs": [
        1
      ],
      "name": "Suzanne M. Crumley",
      "orcid": "0009-0005-7322-021X"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Emily M. Rabjohns",
      "orcid": "0000-0002-4171-6836"
    },
    {
      "affs": [
        3
      ],
      "name": "Luan H. Phan",
      "orcid": "0009-0000-3498-3111"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Di Wu",
      "orcid": "0000-0001-8331-2357"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Russell R. Broaddus",
      "orcid": "0000-0002-8692-273X"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Cyrus Vaziri",
      "orcid": "0000-0002-3081-8685"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Jessica L. Bowser",
      "orcid": "0000-0003-0655-7769"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8h75pbyw6vm69.bib",
  "cited_by": 0,
  "doi": "10.1158/2767-9764.crc-26-0167",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735482/",
  "id": "8h75pbyw6vm69",
  "issns": [
    "2767-9764"
  ],
  "landing_url": "https://doi.org/10.1158/2767-9764.crc-26-0167",
  "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",
      "Cytokines And The Microenvironment"
    ],
    [
      "heading",
      "Endometrial Cancer"
    ],
    [
      "heading",
      "Gynecological Cancers"
    ],
    [
      "heading",
      "Immunology"
    ],
    [
      "heading",
      "Inflamation and the Microenvironment"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "Tumor Microenvironment"
    ],
    [
      "heading",
      "Uterine Cancer"
    ],
    [
      "openalex",
      "1314|Adenosine and Purinergic Signaling"
    ]
  ],
  "openalex": "W7223251883",
  "pdf_url": "https://aacrjournals.org/cancerrescommun/article-pdf/doi/10.1158/2767-9764.CRC-26-0167/3841121/crc-26-0167.pdf",
  "pmcid": "PMC13735482",
  "pmid": "42913692",
  "published": "2026-11-05",
  "publisher": "American Association for Cancer Research",
  "ris": "https://research.draconitic.com/paper/8h75pbyw6vm69.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:09Z",
      "native_id": "PMC13735482",
      "source": "pmc",
      "url": "https://doi.org/10.1158/2767-9764.crc-26-0167"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Cancer Cell CD73 Loss Promotes a Dual Inflammatory and Immunosuppressive Microenvironment in Endometrial Carcinoma",
  "title_text": "Cancer Cell CD73 Loss Promotes a Dual Inflammatory and Immunosuppressive Microenvironment in Endometrial Carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:09Z",
  "url": "https://research.draconitic.com/paper/8h75pbyw6vm69",
  "venue": "Cancer Research Communications",
  "versions": []
}