Related Experiment Video
Updated: Jul 9, 2025
A Macrophage-Tumor Spheroid Co-Invasion Assay
Published on: January 24, 2025
Multicellular tumor spheroid model to study the multifaceted role of tumor-associated macrophages in PDAC
Nadège Bidan1, Garett Dunsmore2, Martina Ugrinic1
1Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, 91400, Orsay, France.
Abstract:
While considerable efforts have been made to develop new therapies, progress in the treatment of pancreatic cancer has so far fallen short of patients' expectations. This is due in part to the lack of predictive in vitro models capable of accounting for the heterogeneity of this tumor and its low immunogenicity. To address this point, we have established and characterized a 3D spheroid model of pancreatic cancer composed of tumor cells, cancer-associated fibroblasts, and blood-derived monocytes. The fate of the latter has been followed from their recruitment into the tumor spheroid to their polarization into a tumor-associated macrophage (TAM)-like population, providing evidence for the formation of an immunosuppressive microenvironment.This 3D model well reproduced the multiple roles of TAMs and their influence on drug sensitivity and cell migration. Furthermore, we observed that lipid-based nanosystems consisting of sphingomyelin and vitamin E could affect the phenotype of macrophages, causing a reduction of characteristic markers of TAMs. Overall, this optimized triple coculture model gives a valuable tool that could find useful application for a more comprehensive understanding of TAM plasticity as well as for more predictive drug screening. This could increase the relevance of preclinical studies and help identify effective treatments.
Insights
A new 3D pancreatic cancer model using tumor cells, fibroblasts, and monocytes reveals how tumor-associated macrophages (TAMs) create an immunosuppressive environment. Lipid nanosystems were found to reduce TAM markers, offering potential for improved drug screening.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- Pancreatic cancer treatment progress is limited by a lack of predictive in vitro models.
- Tumor heterogeneity and low immunogenicity hinder effective therapy development.
- Tumor-associated macrophages (TAMs) play a critical role in the pancreatic tumor microenvironment.
Purpose of the Study:
- To establish and characterize a novel 3D spheroid model of pancreatic cancer.
- To investigate the role of TAMs in pancreatic cancer progression and drug sensitivity.
- To evaluate the impact of lipid-based nanosystems on TAMs.
Main Methods:
- Development of a triple co-culture 3D spheroid model with pancreatic tumor cells, cancer-associated fibroblasts, and monocytes.
- Tracking monocyte differentiation into TAM-like populations within the spheroid.
- Assessing the influence of TAMs on drug sensitivity and cell migration.
- Treatment of the model with lipid-based nanosystems (sphingomyelin and vitamin E).
Main Results:
- The 3D model successfully replicated the immunosuppressive microenvironment created by TAMs.
- TAMs were shown to influence drug sensitivity and cancer cell migration.
- Lipid-based nanosystems modulated macrophage phenotype, reducing key TAM markers.
- The model demonstrated potential for studying TAM plasticity and drug screening.
Conclusions:
- The developed 3D pancreatic cancer model is a valuable tool for understanding TAMs and their role in cancer.
- This model can improve the predictability of preclinical studies and aid in identifying novel cancer treatments.
- Targeting TAMs with agents like lipid nanosystems shows promise for pancreatic cancer therapy.
