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Updated: Apr 28, 2026
A Preclinical Murine Model of Hepatic Metastases
Published on: September 27, 2014
Surgical Resection of Murine PDAC Alters Hepatic Metastases and Immune Microenvironment
Anthony Sorrentino1,2, Carolina Alcantara Hirsch2, Beny Shapiro2
1Department of Surgery, NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA.
Objective:
Identify how surgical resection of pancreatic ductal adenocarcinoma (PDAC) affects systemic minimal residual disease (MRD).
Methods:
Pancreatic tumors were generated by orthotopic implantation of tumor cells into the pancreas of immunocompetent mice. Tumor resection was carried out via distal pancreatectomy and splenectomy. Liver metastases and microenvironment immune changes were analyzed in resected vs. non-resected mice.
Results:
Resection was accompanied by proliferative expansion of liver metastases and an increase in hepatic metastatic burden. Postoperative immune changes predominantly manifested as a time-dependent increase in eosinophils and decrease in neutrophils. The postoperative hepatic eosinophilia was protective of further metastatic progression. The parenchymal findings were detectable in the circulation, and the trends observed in the mouse model modeled those seen in PDAC patients postoperatively.
Conclusion:
Collectively, we describe a preclinical resection model that offers a means to investigate MRD. Using this model, we delineated effects of surgical resection on metastatic outgrowth and uncovered a protective link between the postoperative hepatic eosinophilia and further metastatic progression.
Insights
Surgical resection of pancreatic ductal adenocarcinoma (PDAC) can worsen liver metastases but triggers protective eosinophilia. This preclinical model reveals how surgery impacts minimal residual disease (MRD) and immune responses in PDAC.
Area of Science:
- Oncology
- Immunology
- Surgical Research
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy.
- Understanding the impact of surgical resection on minimal residual disease (MRD) is crucial for improving patient outcomes.
- Existing models for studying PDAC resection and MRD are limited.
Purpose of the Study:
- To establish a preclinical model for investigating the effects of surgical resection on systemic MRD in PDAC.
- To analyze how tumor resection influences liver metastases and the tumor microenvironment.
- To identify immune changes associated with PDAC resection and their impact on metastatic progression.
Main Methods:
- Orthotopic implantation of PDAC cells in immunocompetent mice to generate pancreatic tumors.
- Surgical resection via distal pancreatectomy and splenectomy.
- Analysis of liver metastases and immune cell populations in resected versus non-resected mice.
Main Results:
- Surgical resection led to increased proliferation and burden of liver metastases.
- Postoperative immune changes included increased eosinophils and decreased neutrophils.
- Increased postoperative hepatic eosinophilia correlated with protection against further metastatic progression.
- Observed trends in the mouse model mirrored findings in human PDAC patients.
Conclusions:
- A novel preclinical resection model for PDAC was developed to study MRD.
- Surgical resection impacts metastatic outgrowth and systemic immune responses.
- Postoperative hepatic eosinophilia demonstrates a protective role against PDAC metastatic progression.
