Regulation of breast cancer progression by Treg cells
Description: Breast cancer is the main leading cancer in women worldwide, and while survival has improved, metastatic breast cancer is incurable. Immune cells infiltrate breast tumors, but current immunotherapies are not efficient. Therefore, in order to design better therapies that improve survival, we need to understand how these cells behave in the tumor environment. The main goal of this grant proposal is to investigate the interactions between regulatory T (Treg) cells and myeloid cells, two prominent immune cell populations in breast tumors. Using a mouse model of breast cancer, we have demonstrated that eliminating Treg cells in advanced breast tumors results in significant reduction of the primary tumor and metastatic burden, and that macrophages are necessary to achieve this anti-tumor effect. We hypothesize that Treg cells promote breast cancer progression by modulating the function of macrophages and dendritic cells, two myeloid cell populations with shared origin. In addition, we propose that in the subset of breast cancers with increased immunogenicity, Treg cell ablation will increase the benefit of immune checkpoint blockade strategies. In the present research proposal, we use a combination of mouse modeling, ex vivo cultures, immunohistochemistry, flow cytometry, and single cell RNASequencing to investigate the functional changes in macrophages and dendritic cells caused by Treg cells, and explore the relevance of these mechanisms in human samples and pre-clinical mouse models. Results from the proposed studies will shed light into the immune suppression mechanisms governing breast tumors, and will likely provide targets for intervention.
Funder: American Cancer Society
Amount: $792,000
Funding type: award
Start date: 2022-01-01
End date: 2025-12-31
Investigators: PAULA BOS, Andrea Publow, Charles Clevenger, Magdelana Morgan, Nancy Nicholson, Mikhail Dozmorov, Valentina Robila, Michael Idowu
Institution: Virginia Commonwealth University
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Funded outputs count: 1
Funder award ID: RSG-21-100-01-IBCD
OpenAlex ID: G180721118