{
  "abstract": "Background: Neoadjuvant chemotherapy (NAC) is increasingly incorporated into the management of pancreatic ductal adenocarcinoma (PDAC), yet how treatment regimen and timing reshape the tumour-immune microenvironment remains poorly defined. Methods: Targeted immune transcriptomic profiling was performed using NanoString on spatially annotated tumour, stromal, and immune-enriched regions from resected PDAC specimens from 23 patients, including NAC-treated and treatment-naive cohorts. Key findings were validated and spatially localised using Xenium in situ transcriptomics. Results: NAC induced extensive transcriptional remodelling of the tumour microenvironment in a regimen- and time-dependent manner. Tumours resected shortly after FOLFIRINOX exhibited coordinated upregulation and strong spatial coupling of the CXCL12-CXCR4 axis. These correlations were attenuated or reversed at longer post-treatment intervals and following gemcitabine-based therapy. Disrupted stromal coordination of the CCL2-CCR2 axis further highlighted context-dependent effects of chemotherapy on chemokine signalling. Across regions, NT5E (CD73) expression inversely correlated with CD8A, consistent with spatially restricted T cell exclusion. Conclusions: NAC dynamically reprograms the immunestromal landscape of PDAC in a regimen- and timing-dependent manner, revealing a transient post-chemotherapy window of immune remodelling. The clinical significance of this phenomenon requires further investigation to determine whether temporally optimised integration of immunomodulatory and stroma-targeted therapies with NAC can improve patient outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "School of Science, Faculty of Science Medicine and Health, University of Wollongong, Wollongong, NSW, Australia."
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "E. Minaei"
    },
    {
      "name": "D. Cox"
    },
    {
      "name": "A. S. Thind"
    },
    {
      "name": "G. Tincknell"
    },
    {
      "name": "L. A. Coleman"
    },
    {
      "name": "S. J. Wade"
    },
    {
      "name": "N. Islam"
    },
    {
      "name": "D. Waring"
    },
    {
      "name": "M. Ahuja"
    },
    {
      "name": "J. La Malfa"
    },
    {
      "name": "K. S. Haghighi"
    },
    {
      "name": "M. Ranson"
    },
    {
      "name": "M. Aghmesheh"
    },
    {
      "name": "R. Sluyter"
    },
    {
      "name": "E. M. OReilly"
    },
    {
      "name": "K. L. Vine-Perrow"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9mng4ycq47esn.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.07.749769",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749769v1.full",
  "id": "9mng4ycq47esn",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749769v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7212262935",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749769v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9mng4ycq47esn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:28Z",
      "native_id": "10.64898/2026.09.07.749769",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749769v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Neoadjuvant chemotherapy induces transient, regimen-specific immune stromal reprogramming in pancreatic ductal adenocarcinoma",
  "title_text": "Neoadjuvant chemotherapy induces transient, regimen-specific immune stromal reprogramming in pancreatic ductal adenocarcinoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:28Z",
  "url": "https://research.draconitic.com/paper/9mng4ycq47esn",
  "venue": "bioRxiv",
  "versions": []
}