# Overcoming stress driven suppression of the anti-tumor immune response in cancer - understanding the MDSC piece of the puzzle

> **NIH NIH F32** · ROSWELL PARK CANCER INSTITUTE CORP · 2020 · $67,446

## Abstract

SUMMARY: Chronic stress can suppress immunity. However, details about how stress affects tumor growth
and anti-tumor immunity are still missing or poorly understood. Myeloid derived suppresser cells (MDSCs) are
increasingly recognized as critical players in tumor immunology because, in addition to their fundamental roles
in suppressing effector NK cells, CD8+ T cells and CD4+ T cells, they also play a direct role in tumor growth,
differentiation and metastasis. Exactly how stress, particularly adrenergic stress, affects MDSCs is largely
unknown. Addressing this piece of the puzzle is the overall goal of this application. The hypothesis of this
proposal is that increased level of norepinephrine during chronic stress activates β- adrenergic receptor (β-
AR) signaling in MDSCs and increases pro-tumor functions and survival of MDSCs, both in the primary tumor
microenvironment and in metastatic sites (lung and bone marrow).
We will address this hypothesis in two specific aims: Aim 1: To test the hypothesis that β2-AR signaling
regulates MDSC distribution, accumulation and function in tumors and Aim 2: To determine
mechanisms by which β2-AR signaling alters MDSC survival in the tumor. We will use metastatic 4T1
and non-metastatic AT-3 murine breast cancer models. 4T1 is a clinically relevant model of breast cancer that
is implanted orthotopically in the mammary gland and metastasizes to the lung, as well as other sites and is
known to induce MDSC accumulation. AT-3 tumor cell line was established from a primary mammary gland
carcinoma of an MMTV-PyMT transgenic mouse model and induces CD11b+Gr-1+ MDSC response after
implantation. We will use three different strategies to reduce and/or block adrenergic signaling. These
approaches include genetic (β2AR-/- mice compared to littermate wild-type controls), pharmaceutical (beta-AR
blockers compared to PBS) and physiological (cold housing versus warm housing). Altogether, my proposed
research will provide an important research experience that will reveal the key role of β2-adrenrgic signaling in
tumor growth in general, and immune-inhibitory functions of MDSCs in particular, and reveal new mechanisms
by which chronic stress promotes tumor growth.
This Training Grant will enhance my ability to experience many other critical career-building opportunities that
will greatly increase my chances of obtaining a K99/R00 award and my own independent laboratory in the
future. It can also help me to take advantage of opportunities to learn new techniques in complimentary fields,
such as genomic applications, which will expand my expertise and independence.

## Key facts

- **NIH application ID:** 9909548
- **Project number:** 1F32CA239356-01A1
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** Hemn Mohammadpour
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 1
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9909548

## Citation

> US National Institutes of Health, RePORTER application 9909548, Overcoming stress driven suppression of the anti-tumor immune response in cancer - understanding the MDSC piece of the puzzle (1F32CA239356-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9909548. Licensed CC0.

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