# Modeling Immune Cell Recruitment and its Impact on Triple Negative Breast Cancer Recurrence in the Irradiated Microenvironment

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2021 · $34,064

## Abstract

PROJECT SUMMARY
Approximately half of triple negative breast cancer (TNBC) patients receive breast conserving therapy, which
includes irradiating the primary tumor site. Although this therapy improves prognosis overall, patients continue
to experience locoregional recurrences at high rates. The mechanisms controlling recurrence following therapy
are poorly understood. Previous research suggests that normal tissue radiation damage may be correlated to
recurrence. Pre-clinical studies have shown that tumor cells migrate into irradiated mammary tissue and that
macrophages play a critical role in the tumor cell recruitment process. While blockade of macrophage infiltration
was shown to eliminate tumor cell migration to irradiated sites, the impact of macrophage phenotype has not
been investigated. Macrophages with a wound healing phenotype (M2) are known to promote tumor growth and
progression, but whether M2 macrophages influence tumor cell recruitment and proliferation in irradiated tissues
is unknown. The central hypothesis of this proposal is that radiation damage in the tissue microenvironment
promotes a pre-metastatic niche through immunosuppressive cell infiltration. I will test this hypothesis using pre-
clinical orthotopic breast cancer models as well as organoids to study the normal tissue response to radiation
and its influence on recurrence.
This project is guided by two specific aims: 1) To characterize macrophage phenotypes associated with RT-
induced recurrence and 2) to identify targetable secreted factors that contribute to tumor cell recruitment in
irradiated tissues. In Aim 1, I will rigorously examine the immune cell infiltrate into irradiated mammary tissue
using flow cytometry. To confirm the importance of M2 macrophages in recurrence, I will develop an M2
macrophage-depleted mouse model by blocking polarization with small molecule inhibitors or monoclonal
antibodies. Finally, I will determine the impact of M2 macrophage depletion on tumor cell recruitment to irradiated
tissues. In Aim 2, I will use an organoid model developed by our laboratory that recapitulates pre-clinical
observations. I will analyze secreted pro-tumor factors by co-culturing organoids with macrophages, tumor cells,
and CD8+ T cells and characterizing secreted cytokines in conditioned media. I will then evaluate how these
factors contribute to tumor cell recruitment in vivo. This study will establish the conditions that lead to recurrence
following radiotherapy, including composition of macrophage infiltrate and mechanisms of tumor regrowth, which
will have significant implications for TNBC patients vulnerable to recurrence.

## Key facts

- **NIH application ID:** 10157580
- **Project number:** 1F31CA254311-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Benjamin Christian Hacker
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,064
- **Award type:** 1
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157580

## Citation

> US National Institutes of Health, RePORTER application 10157580, Modeling Immune Cell Recruitment and its Impact on Triple Negative Breast Cancer Recurrence in the Irradiated Microenvironment (1F31CA254311-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10157580. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*