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Updated: Jun 10, 2025
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Dynamic reciprocal interactions between activated T cells and tumor associated macrophages drive macrophage
Erika Heninger1, Matthew Thomas Breneman1, Emma Elizabeth Recchia1
1Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
Abstract:
Tumor-associated macrophages (TAMs) have been implicated as a tumor microenvironment (TME) cell population, which may be playing a vital role in the inhibition of effective T cell responses in the prostate TME. In this manuscript, we leverage a novel microscale cell culture platform, known as Stacks, to investigate mono-, co-, and tri-culture TME models comprised of prostate tumor cell lines, primary macrophages, and autologous T cells from patients with prostate cancer. Through multiplexed analysis of these multi-cellular prostate tumor models, we capture a dynamic interaction between primary TAMs and activated T cells that resulted in reciprocal proinflammatory activation of both cell populations upon interaction. These findings suggest that activated T cells are capable of reprogramming immunosuppressive TAMs in the context of prostate tumor models and that TAM reprogramming may play a key supportive role in restoring proinflammatory T cell tumor responses in the prostate TME.
Insights
Activated T cells can reprogram immunosuppressive tumor-associated macrophages (TAMs) in prostate cancer models. This reprogramming supports restoring anti-tumor T cell responses within the tumor microenvironment (TME).
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) and are often implicated in suppressing effective T cell responses in prostate cancer.
- Understanding the dynamic interactions between immune cells within the prostate TME is crucial for developing effective cancer immunotherapies.
Purpose of the Study:
- To investigate the interactions between prostate tumor cells, macrophages, and T cells using a novel microscale cell culture platform.
- To determine if activated T cells can reprogram immunosuppressive TAMs in the context of prostate cancer models.
Main Methods:
- Utilized a novel microscale cell culture platform (Stacks) to create mono-, co-, and tri-culture models of the prostate TME.
- Models included prostate tumor cell lines, primary macrophages, and autologous T cells from prostate cancer patients.
- Employed multiplexed analysis to capture dynamic cellular interactions.
Main Results:
- Observed a dynamic interaction between primary TAMs and activated T cells in multi-cellular prostate tumor models.
- Demonstrated reciprocal proinflammatory activation of both TAMs and T cells upon interaction.
- Showcased the ability of activated T cells to reprogram immunosuppressive TAMs.
Conclusions:
- Activated T cells can reprogram immunosuppressive TAMs within prostate tumor models.
- TAM reprogramming by T cells may play a supportive role in restoring proinflammatory T cell responses against prostate tumors.
- These findings highlight a potential therapeutic strategy targeting TAM reprogramming in prostate cancer.
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