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Updated: Sep 18, 2025
Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
Published on: January 17, 2025
Precision Medicine: IL-1RA and Pancreatic Cancer Organoids
Annah G Morgan1, Michelle F Griffin1,2, Michael T Longaker1,2
1Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract:
Cancer organoids have emerged as transformative models for studying tumor biology and therapeutic responses due to the ability to replicate the complexity of the tumor microenvironment (TME). Tumor organoids recapitulate the genetic and phenotypic diversity of cancers, making them invaluable for investigating mechanisms of resistance and identifying novel therapeutic targets. Patient-derived organoids (PDOs) allow specific treatment methods to be designed based on the properties of each individual tumor in vitro. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with an immunosuppressive nature. PDAC has a poor prognosis, with the survival rates of metastatic PDAC being improved only minimally over the last few decades. In this study, we demonstrate the antitumor effects of an IL-1 receptor antagonist (IL-1RA) in murine and human PDAC organoids. By reducing the burden of suppressive tumor elements like CAFs, IL-1RA treatment facilitates better immune cell access and response.
Insights
Interleukin-1 receptor antagonist (IL-1RA) shows antitumor effects in pancreatic ductal adenocarcinoma (PDAC) organoid models. This cancer therapy enhances immune cell access by reducing suppressive tumor elements, offering new treatment strategies.
Area of Science:
- Oncology
- Immunology
- Biomedical Engineering
Background:
- Cancer organoids accurately model the tumor microenvironment (TME), aiding research into tumor biology and treatment responses.
- Patient-derived organoids (PDOs) enable personalized in vitro cancer treatment design.
- Pancreatic ductal adenocarcinoma (PDAC) is aggressive, immunosuppressive, and has a poor prognosis, especially in metastatic stages.
Purpose of the Study:
- To investigate the antitumor effects of an IL-1 receptor antagonist (IL-1RA) in PDAC.
- To evaluate IL-1RA's impact on immune cell infiltration within PDAC models.
Main Methods:
- Utilized murine and human PDAC organoid models.
- Assessed the effects of IL-1RA treatment on tumor organoids and associated suppressive elements.
Main Results:
- Demonstrated significant antitumor effects of IL-1RA in PDAC organoids.
- Showed that IL-1RA reduces cancer-associated fibroblasts (CAFs) and other suppressive tumor components.
- Facilitated improved immune cell access and response within the tumor microenvironment.
Conclusions:
- IL-1RA exhibits therapeutic potential against PDAC.
- Targeting IL-1 signaling can overcome tumor-induced immunosuppression.
- IL-1RA may enhance immunotherapy efficacy in PDAC by modulating the TME.
