# Regulation of tumor associated macrophages by STAT5 in breast cancer

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2020 · $31,807

## Abstract

ABSTRACT
Despite advances in therapies for breast cancer, this disease remains a significant cause of mortality in
women. Triple negative breast cancer (TNBC) patients have the worst prognosis and survival outcome relative
to other breast cancer subtypes. Therefore, much interest surrounds the development of systemic novel
targeted therapeutics; however, little is known about how these drugs affect the surrounding non-tumor cells
within the tumor microenvironment. Understanding how systemically-delivered breast cancer-targeted
therapies interact with non-tumor cells such as infiltrating macrophages is necessary for elucidating how cells
become drug resistant and for developing more effective and durable therapies in cancer patients. The Janus
Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) signaling pathway is activated in TNBC
and is an attractive therapeutic target. New therapies in clinical trials aim to inhibit JAK/STAT signaling
components, such as STAT5, to turn off this “switch” in tumors that signal for growth and proliferation1. We find
this component of the JAK/STAT signaling pathway is also robustly activated in macrophages in response to
TNBC tumor cell-derived factors. We hypothesize that although inhibition of the JAK/STAT pathway may act on
the primary tumor directly, the inhibitor alters a delicate balance in the microenvironment that influences
infiltrating macrophages from an anti-tumor immune response to a pro-inflammatory and thus, pro-tumorigenic
response. Our goal is to define the functional contributions of STAT5 to macrophage polarization within the
tumor microenvironment and to macrophage-mediated resistance of mammary tumors to JAK/STAT inhibition.
To address these questions, this proposal will employ use of mouse mammary tumor models and clinically-
relevant JAK/STAT inhibition strategies to delineate the signaling components responsible for creating this shift
from tumor-hostile to tumor-friendly, as well as, provide rationale for potential therapeutic interventions to
maintain an anti-tumor response against TNBC.

## Key facts

- **NIH application ID:** 9830591
- **Project number:** 5F31CA220746-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Emily A Irey
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,807
- **Award type:** 5
- **Project period:** 2017-12-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830591

## Citation

> US National Institutes of Health, RePORTER application 9830591, Regulation of tumor associated macrophages by STAT5 in breast cancer (5F31CA220746-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9830591. Licensed CC0.

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