{
  "abstract": "Pancreatic ductal adenocarcinoma (PDAC) is largely resistant to immune checkpoint blockade (ICB) due to its highly immunosuppressive tumor microenvironment. How to switch the “immune-cold” microenvironment to “immune hot” one is a clinical unmet need. We recently generated a genetically engineered PDAC mouse model (KAR) by combining K-Ras mutation and AT-rich interactive domain-containing protein 1A (ARID1A) inactivation in the pancreas. Compared to the KPC (K-Ras mutation + p53 inactivation) tumors, KAR tumors express higher C-X-C chemokine receptor 2 (CXCR2) and have more CXCR2+ neutrophils infiltration. Our previous study demonstrated that activation of CXCR2 by its cognate ligands promotes proliferation and drug resistance in PDAC cells. In addition, increase in tumor-associated neutrophils and high neutrophil-to-lymphocyte ratio are associated with worse prognosis in PDAC patients. Here, we developed a monoclonal antibody against human CXCR2 (huCXCR2-Ab) and tested its therapeutic effect in cells and in animals. Treatment with huCXCR2-Ab inhibited IL-8–induced downstream signaling, and the proliferation of human PDAC cancer cells. In addition, huCXCR2-Ab suppressed PDAC growth in an orthotopic nude mouse model. We next developed a monoclonal antibody against mouse CXCR2 (muCXCR2-Ab) and investigated its immune regulatory effect in vivo. We showed that muCXCR2-Ab reduced tumor burden, increased CD8⁺ T-cell infiltration, and decreased immunosuppressive neutrophils in the KAR mice. Moreover, muCXCR2-Ab augments the therapeutic efficacy of anti-PD-L1. Thus, dual targeting of CXCR2+ tumor cells and tumor-associated neutrophils remodels tumor microenvironment and enhances immunotherapy response in ARID1A-deficient PDAC, providing a new strategy for precision therapy of PDAC.",
  "abstract_shown": true,
  "affiliations": [
    "National Institute of Cancer Research, National Health Research Institutes"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tzu-Lei Kuo"
    },
    {
      "affs": [
        0
      ],
      "name": "Kuan-Chung Hsiao"
    },
    {
      "affs": [
        0
      ],
      "name": "Ko-Jiunn Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Li-Tzong Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Wen-Chun Hung"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6s15832m9fcc5.bib",
  "cited_by": 0,
  "doi": "10.1007/s00262-026-04498-6",
  "fulltext_url": "https://doi.org/10.1007/s00262-026-04498-6",
  "id": "6s15832m9fcc5",
  "issns": [
    "1432-0851",
    "0340-7004"
  ],
  "landing_url": "https://doi.org/10.1007/s00262-026-04498-6",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
    ],
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7169868562",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/6s15832m9fcc5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:06Z",
      "native_id": "e7262bedf3f5445cb1844ee42dbacada",
      "source": "doaj",
      "url": "https://doi.org/10.1007/s00262-026-04498-6"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "Dual inhibition of tumor cells and tumor-associated neutrophils by anti-CXCR2 antibodies suppresses tumor growth and augments immunotherapy efficacy in ARID1A-deficient pancreatic cancer",
  "title_text": "Dual inhibition of tumor cells and tumor-associated neutrophils by anti-CXCR2 antibodies suppresses tumor growth and augments immunotherapy efficacy in ARID1A-deficient pancreatic cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:06Z",
  "url": "https://research.draconitic.com/paper/6s15832m9fcc5",
  "venue": "Cancer Immunology, Immunotherapy",
  "versions": []
}