# Epigenetic regulation of myeloid regulatory cell accumulation in the tumor microenvironment

> **NIH NIH F31** · AUGUSTA UNIVERSITY · 2022 · $34,567

## Abstract

Project Summary
Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature myeloid
cells that massively accumulate in cancer patients, including colorectal cancer patients. MDSCs
not only exhibit potent immune suppressive activity to inhibit T and NK cell activation and
functions to promote tumor immune evasion but also secret mediators to directly promote tumor
growth. Our recent published data determined that MDSCs inhibit CTL functions through both
PD-L1-dependent and PD-L1- independent mechanisms. Anti-PD-L1 immunotherapy only
blocks PD-L1-dependent immune suppression. Our data thus indicate that MDSCs can inhibit
CTL function even in the presence of anti-PD-1 blockade. Considering the nature of massive
accumulation of MDSCs in the tumor microenvironment, the PD-L1-independent immune
suppression by MDSCs may at least in part underlie colorectal cancer non-response to ICI
immunotherapy. However, this is a hypothesis that remains to be tested. MDSC accumulation is
due to an increase of tumor-induced myeloid cell differentiation. However, emerging data
indicate that dysregulated cell death pathways also plays a key role in MDSC accumulation. Our
preliminary studies identified the IL6-STAT3-DNMT epigenetic axis impairs the TNF?-RIP1
necroptosis in MDSCs to main MDSC survival and accumulation in tumor-bearing mice. Our
objects in this project are to 1) elucidate the molecular mechanism underlying epigenetic
repression of Tnf expression by the autocrine IL6-STAT3-DNMT axis in MDSCs in colon
carcinoma in vivo, and 2) to test the hypothesis that targeting IL6 is effective to promote MDSC
necroptosis to suppress MDSC accumulation to overcome colon cancer resistance to anti-PD-1
immunotherapy. Successful completion of the proposed studies will provide mechanistic insight
into epigenetic regulation of MDSC accumulation in colon cancer and has a great potential to
develop a targeted therapy to overcome colon cancer resistance to anti-PD-1 immunotherapy.

## Key facts

- **NIH application ID:** 10323650
- **Project number:** 5F31CA257212-02
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Alyssa Merting
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $34,567
- **Award type:** 5
- **Project period:** 2020-12-18 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10323650

## Citation

> US National Institutes of Health, RePORTER application 10323650, Epigenetic regulation of myeloid regulatory cell accumulation in the tumor microenvironment (5F31CA257212-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10323650. Licensed CC0.

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