{
  "abstract": "Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited responsiveness to immune checkpoint blockade. Here, we identify endoplasmic reticulum oxidoreductase 1 alpha (ERO1α; ERO1A), a key regulator of oxidative protein folding, as a determinant of tumor immunogenicity and immunotherapy response in TNBC. Unbiased proteomic profiling demonstrated that ERO1α deficiency remodels the TNBC glycoproteome, leading to enrichment of pathways associated with immune signaling. Although ERO1α loss did not affect tumor cell growth, it reshaped the immune tumor microenvironment, enhancing antigen presentation, altering myeloid-cell composition, and modulating PD-1/PD-L1–associated signaling. Functionally, ERO1α deficiency sensitized otherwise refractory TNBC tumors to PD-1 blockade, resulting in durable tumor regression in immunocompetent hosts. In contrast, ERO1α deletion in bone marrow–derived immune cells had minimal effects on tumor growth or therapeutic response, supporting an ERO1α tumor-intrinsic mechanism. Pharmacologic inhibition of ERO1α with the novel small-molecule inhibitor I29 phenocopied ERO1α genetic deletion and enhanced the efficacy of anti–PD-1 therapy. Together, these findings identify ERO1α-dependent glycoproteome remodeling as a regulator of antitumor immunity and a therapeutically actionable mechanism of immune checkpoint responsiveness in TNBC.",
  "abstract_shown": true,
  "affiliations": [
    "Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy",
    "Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy",
    "Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy",
    "IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy",
    "Cogentech SRL Benefit Corporation, Milan, 20139, Italy",
    "Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy",
    "Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; Bioinformatics Core Unit, Institute of Oncology Research (IOR), Bellinzona, Switzerland",
    "U.O. Patologia Mammaria e Tumori Cerebrali, Azienda Socio-Sanitaria Territoriale, Cremona, Italy",
    "Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; IRCCS Humanitas Research Hospital, Milan, Italy",
    "Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy; Corresponding author. Istituto di Ricerche Farmacologiche Mario Negri IRCCS Via Mario Negri 2, 20156, Milano, Italy."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Alessandro Cherubini"
    },
    {
      "affs": [
        1
      ],
      "name": "Ersilia Varone"
    },
    {
      "affs": [
        1
      ],
      "name": "Sara Irene Malandrin"
    },
    {
      "affs": [
        1
      ],
      "name": "Alice Marrazza"
    },
    {
      "affs": [
        2
      ],
      "name": "Giorgia Maria Renna"
    },
    {
      "affs": [
        1
      ],
      "name": "Serena Germani"
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    {
      "affs": [
        1
      ],
      "name": "Stefano Fumagalli"
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    {
      "affs": [
        3
      ],
      "name": "Angela Bachi"
    },
    {
      "affs": [
        4
      ],
      "name": "Angela Cattaneo"
    },
    {
      "affs": [
        5
      ],
      "name": "Michele Retini"
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    {
      "affs": [
        5
      ],
      "name": "Giovanni Piersanti"
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    {
      "affs": [
        6
      ],
      "name": "Marco Bolis"
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    {
      "affs": [
        1
      ],
      "name": "Ilaria Craparotta"
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    {
      "affs": [
        1
      ],
      "name": "Arianna Vallerga"
    },
    {
      "affs": [
        1
      ],
      "name": "Chiara Grasselli"
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    {
      "affs": [
        7
      ],
      "name": "Manuela Milani"
    },
    {
      "affs": [
        7
      ],
      "name": "Daniele Generali"
    },
    {
      "affs": [
        8
      ],
      "name": "Augusto Bleve"
    },
    {
      "affs": [
        9
      ],
      "name": "Ester Zito"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0dxqsw67h8pzr.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104451",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2213231726004507",
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  "language": "en",
  "licence": "CC-BY-NC-4.0",
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      "heading",
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      "lcc",
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  "pmcid": "PMC13722565",
  "pmid": "42925724",
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/0dxqsw67h8pzr.ris",
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      "first_seen": "2026-10-30T13:47:21Z",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Redox biology and oxidative stress",
      "subfield": "molecular-biology"
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  "title": "Targeting ERO1α triggers tumor immunosurveillance in triple-negative breast cancer",
  "title_text": "Targeting ERO1α triggers tumor immunosurveillance in triple-negative breast cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:21Z",
  "url": "https://research.draconitic.com/paper/0dxqsw67h8pzr",
  "venue": "Redox Biology",
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}