Dynamic reciprocal interactions between activated T cells and tumor associated macrophages drive macrophage reprogramming and proinflammatory T cell migration within prostate tumor models
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.
Authors
- Aaron M. LeBeau (ORCID: https://orcid.org/0000-0003-3802-7789)
- Erika Héninger (ORCID: https://orcid.org/0000-0003-0166-9972)
- Marina N. Sharifi (ORCID: https://orcid.org/0000-0003-0128-3033)
- Emma E. Recchia (ORCID: https://orcid.org/0000-0002-6948-0220)
- Sheena C. Kerr (ORCID: https://orcid.org/0000-0002-4404-3382)
- Matthew T. Breneman (ORCID: https://orcid.org/0000-0003-3399-7831)
- Reyna Elvan Dogru
- David Kosoff (ORCID: https://orcid.org/0000-0001-8559-6357)
Institutions
- University of Wisconsin–Madison (US)
- University of Wisconsin Carbone Cancer Center (US)
- William S. Middleton Memorial Veterans Hospital (US)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1038/s41598-024-75265-9
- Citations
- 4
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.96
Funders
- U.S. Department of Defense
- U.S. Department of Veterans Affairs
- Office of Research and Development
- University of Wisconsin Carbone Cancer Center
- DOD Prostate Cancer Research Program