{
  "abstract": "Cancer cell-intrinsic epithelial-mesenchymal plasticity (EMP) drives carcinoma progression through increased intratumoral heterogeneity and an immunosuppressive tumor microenvironment (TME). Specifically, EMP activation in murine mammary carcinomas results in exclusion of CD8+ T-cells and recruitment of immunosuppressive M2-like macrophages, resulting in resistance to anti-CTLA-4 immune checkpoint blockade (ICB) therapy. Notably, mixed E-qM tumors in which only 10% of cancer cells have activated EMP are resistant anti-CTLA-4 immune checkpoint blockade (ICB) therapy. This suggests that minority fractions of qM cancer cells could, in theory, exert immunosuppressive effects on surrounding E cancer and immune cells to shield the entire heterogeneous tumor against immune attack. However, this has not yet been demonstrated. Here, we use spatial transcriptomic profiling to demonstrate that mixed E-qM tumors assemble immunosuppressive cellular niches. Furthermore, E cancer cells within mixed E-qM tumors experience long-term MHC-I downregulation leading to resistance to elimination by CD8+ T-cells. This is associated with the exclusion of T-cells from the tumor core and a dysfunctional phenotype in the remaining CD8+ T-cells. qM cancer cells recruit immunosuppressive M2-like macrophages to mixed tumors, which further downregulates E cancer cell-intrinsic MHC-I levels. Finally, we demonstrate that human triple-negative breast cancers with increased EMP activation exclude T-cells from the tumor core. Together, these findings reveal that qM cancer cells modulate the immune infiltrate of mixed tumors, promoting MHC-I downregulation and evasion of immunological control by CD8+ T-cells.",
  "abstract_shown": true,
  "affiliations": [
    "Cornell University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "K. M. Bakhle"
    },
    {
      "name": "A. Stephanou"
    },
    {
      "name": "S. Sahoo"
    },
    {
      "name": "I. Ntekas"
    },
    {
      "name": "K. Priebe"
    },
    {
      "name": "M. Rahman"
    },
    {
      "name": "R. Puri"
    },
    {
      "name": "S. Butler"
    },
    {
      "name": "P. Schweitzer"
    },
    {
      "name": "S. Chandraganti"
    },
    {
      "name": "M. K. Jolly"
    },
    {
      "name": "I. De Vlaminck"
    },
    {
      "name": "P. Sethupathy"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Dongre"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5bzphrbxrhqyc.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.17.759751",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759751v1.full",
  "id": "5bzphrbxrhqyc",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759751v1",
  "language": null,
  "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": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7222969884",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759751v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5bzphrbxrhqyc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:36Z",
      "native_id": "10.64898/2026.10.17.759751",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759751v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "MHC-I downregulation is associated with immune-evasion in breast cancers with heterogeneous activation of epithelial-mesenchymal plasticity",
  "title_text": "MHC-I downregulation is associated with immune-evasion in breast cancers with heterogeneous activation of epithelial-mesenchymal plasticity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:36Z",
  "url": "https://research.draconitic.com/paper/5bzphrbxrhqyc",
  "venue": "bioRxiv",
  "versions": []
}