# Progesterone promotes mammary gland tumorigenesis through immunosuppressive effects on dendritic cells

> **NIH NIH F30** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $34,542

## Abstract

ABSTRACT
Breast cancer is the second most common cause of cancer-related death and most common cancer occurring
in females in the U.S. Numerous large-scale clinical trials have demonstrated that use of exogenous progestins
(synthetic progesterone [P4]) increases the risk of invasive breast cancer in females. Although it has been
clearly established in the literature that P4 plays a role in the development of human breast cancer, the
mechanism by which P4 promotes breast cancer tumorigenesis remains unknown. Recently, we reported a link
between progesterone receptor (PR) and immune signaling pathways. Our recent publications have
demonstrated that P4/PR can repress type I interferon signaling pathways in human breast cancer cells. Given
these findings, we sought to investigate whether P4/PR drive immunomodulation in the mammary gland to
promote formation of mammary gland tumors. Therefore, the central hypothesis of this proposal is that P4
and PR decrease recruitment and function of DCs in the mammary gland, which promotes immunosuppression
and subsequent development and growth of mammary gland tumors. We will address this hypothesis through
the following specific aims: 1) Define the mechanism by which P4 treatment and PR expression affect DC
recruitment to the murine mammary gland and PR+ mammary gland tumors; 2) Characterize the maturation
and activity state of DCs isolated from P4-treated PR+ mammary gland tumors; and 3) Determine the
contribution of P4-mediated DC suppression to mammary gland tumor growth. For aim 1, we will utilize single
cell RNA sequencing (scRNA-seq) to determine if P4 affects the release of cytokines involved in DC
recruitment to mammary gland tumor cells. In aim 2, we will determine how P4 treatment affects the activity
and function of tumor-infiltrating DCs using syngeneic tumor models, in which markers will be measured via
scRNA-seq, flow cytometry, and T cell proliferation assays. Aim 3 will utilize transgenic mouse models to
determine whether depletion of DCs impacts P4’s growth-promoting effects on mammary gland tumors.
Successful completion of the proposed work will provide novel insight into immune tolerance mechanisms
promoting the development and growth of breast cancers. Additionally, it will provide a rationale to target
P4/PR signaling with anti-progestins to promote DC function and enhance immune-mediated elimination of
tumor cells.

## Key facts

- **NIH application ID:** 10464253
- **Project number:** 1F30CA271796-01
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Lauryn Rose Werner
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $34,542
- **Award type:** 1
- **Project period:** 2022-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464253

## Citation

> US National Institutes of Health, RePORTER application 10464253, Progesterone promotes mammary gland tumorigenesis through immunosuppressive effects on dendritic cells (1F30CA271796-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10464253. Licensed CC0.

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