# Regulation of IL-4 macrophage polarization by SWI/SNF family complexes

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2022 · $40,379

## Abstract

Project Summary/Abstract
Macrophage polarization into activated M1 (inflammatory) and M2 (immunosuppressive) subsets is critical to
immune function. The failure to properly regulate polarization can lead to chronic inflammation, autoimmunity,
and cancer progression. In malignancy, the polarization of immunosuppressive tumor-associated macrophages
(TAMs) is a strong predictor of prognosis for many solid tumors and has been a significant hurdle to
immunotherapies designed to activate strong anti-cancer T cell responses, including immune checkpoint
blockade (ICB) and CAR-T cell therapies. Macrophage polarization is driven by signal-induced STAT
transcription factors, which cooperate with SWI/SNF-family ATP-dependent chromatin remodeling complexes
to alter DNA accessibility and to create sustained gene expression changes. In preliminary studies, I have
found that SWI/SNF activity is critical to M2 macrophage polarization, and we believe this dependency has the
potential to be therapeutically targeted to prevent immunosuppressive TAM accumulation in solid tumors. We
hypothesize that SWI/SNF-family chromatin remodelers (BAF/PBAF/GBAF) are critical to the acquisition of
immunosuppressive macrophage phenotypes and play differential roles in generating chromatin accessibility
during polarization by IL-4. We expect that these remodelers enable gene activation by generating DNA
accessibility across the genome for polarization-induced STAT TF binding sites. To address this central
hypothesis, we will inhibit SWI/SNF activity, then identify the SWI/SNF dependencies of IL-4 induced M2
polarization via functional, transcriptomic, and epigenomic profiling. We will also validate the role of SWI/SNF
inhibition on the tumor microenvironment in an immunocompetent mouse model of cancer. Through this
proposal, we aim to leverage the contribution of SWI/SNF chromatin remodelers to control TAM phenotypes in
cancer. Understanding the epigenetic features that regulate M2 polarization will provide opportunities to
improve patient outcomes by reducing the anti-inflammatory polarization phenotypes of TAMs. As a result, our
work has the potential to help turn immunologically “cold” tumors “hot.”

## Key facts

- **NIH application ID:** 10464334
- **Project number:** 1F31AI161906-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** COURTNEY CHAMBERS
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,379
- **Award type:** 1
- **Project period:** 2022-08-17 → 2023-05-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464334

## Citation

> US National Institutes of Health, RePORTER application 10464334, Regulation of IL-4 macrophage polarization by SWI/SNF family complexes (1F31AI161906-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10464334. Licensed CC0.

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