# HUNK Regulation of IL-4

> **NIH NIH R03** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $158,500

## Abstract

PROJECT SUMMARY
Metastatic breast cancer is driven by pro-tumor immune responses. No immuno-agents are currently approved
for use in breast cancer and the ability of these agents to mitigate disease is currently unclear. Consequently,
developing a clear understanding of the mechanisms by which immune cells are regulated during breast cancer
progression is critical for the successful application of immunotherapy for breast cancer. We propose to evaluate
a protein kinase called Hormonally-upregulated Neu-associated Kinase (HUNK), a tumor and metastasis
promoting factor, as a target that alters immune response in metastatic breast cancer. Immune cells called tumor
associated macrophages (TAMs) are recruited to the tumor microenvironment through paracrine signaling with
tumor cells, which results in an immune suppressive phenotype and metastatic progression. Previous studies
show that TAMs exhibit an “alternatively” activated phenotype consistent with M2-type polarization and identify
IL-4 as a major cytokine that induces the M2-phenotype. We provide evidence that HUNK regulates IL-4
production in mammary tumor cells, which results in a reduction in TAMs in the tumor microenvironment. We
hypothesize that HUNK regulates IL-4 production in mammary tumor cells, which in turn, drives alternative
activation of macrophages (ie presence of TAMs) in the tumor microenvironment. These studies would be the
first to describe an immune related function for HUNK where tumor cell intrinsic signaling driven by HUNK
regulates paracrine signaling to TAMs.

## Key facts

- **NIH application ID:** 10046490
- **Project number:** 1R03CA245774-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Elizabeth Yeh
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $158,500
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046490

## Citation

> US National Institutes of Health, RePORTER application 10046490, HUNK Regulation of IL-4 (1R03CA245774-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10046490. Licensed CC0.

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