{
  "abstract": "Lymph node (LN) microenvironmental signals promote chronic lymphocytic leukemia (CLL) cell survival, proliferation, and treatment resistance. We previously developed a 3D culture model that recapitulates key features of this protective LN niche. Using single-cell RNA sequencing of ex vivo paired peripheral blood and LN samples, together with matched patient-derived CLL spheroids, we investigated how microenvironmental cues shape CLL phenotypes and their response to ibrutinib. A total of 3 functional CLL states (resting, activated, proliferating) were identified, with expanded populations of activated and proliferating subsets in 3D cultures. After 5 days of in vitro ibrutinib treatment, CLL cells shifted toward a resting phenotype, reflecting published responses in patients at 6 months. Activated CLL cells showed relative resistance to ibrutinib, associated with TLR9-MALT1-MYC pathway activation. The 3D model recapitulated tissue-specific T cell phenotypes observed in patients, and computational analyses predicted several T-to-CLL cell-mediated interactions supporting the LN niche. Collectively, these data reveal distinct ibrutinib responses among CLL subsets and establish the 3D model as a physiologically relevant platform.",
  "abstract_shown": true,
  "affiliations": [
    "Amsterdam UMC"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "M. V. Haselager"
    },
    {
      "name": "D. Lashgari"
    },
    {
      "name": "A. Jongejan"
    },
    {
      "name": "J. L. Roos"
    },
    {
      "name": "M. Dijkema"
    },
    {
      "name": "J. Dubois"
    },
    {
      "name": "F. S. Peters"
    },
    {
      "name": "A. P. Kater"
    },
    {
      "name": "P. D. Moerland"
    },
    {
      "affs": [
        0
      ],
      "name": "E. Eldering"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1zrv6me5t4aam.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.31.763314",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763314v1.full",
  "id": "1zrv6me5t4aam",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763314v1",
  "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": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763314v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1zrv6me5t4aam.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:21:11Z",
      "native_id": "10.64898/2026.10.31.763314",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763314v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Single-cell characterization of 3D CLL spheroid model that recapitulates lymph node microenvironment-driven phenotypes and in vivo drug responses to ibrutinib",
  "title_text": "Single-cell characterization of 3D CLL spheroid model that recapitulates lymph node microenvironment-driven phenotypes and in vivo drug responses to ibrutinib",
  "type": "preprint",
  "updated_at": "2026-11-05T00:20:38Z",
  "url": "https://research.draconitic.com/paper/1zrv6me5t4aam",
  "venue": "bioRxiv",
  "versions": []
}