# Negative regulation of myeloid-derived suppressive cells in cancer

> **NIH NIH R01** · WISTAR INSTITUTE · 2020 · $547,478

## Abstract

Myeloid cells are critical component of tumor microenvironment. Abnormal differentiation of myeloid cells
is now considered a major immunological hallmark of cancer. One of the most prominent changes in the
myeloid compartment in cancer is the expansion of pathologically activated relatively immature myeloid
cells with the potent ability to suppress immune responses – myeloid-derived suppressor cells (MDSC).
In recent years, MDSC emerged as critically important regulators that suppress anti-cancer immunity and
limit the efficacy of cancer immune therapy. Therefore, understanding of the mechanisms regulating
MDSC function is of fundamental and translational importance. As only small proportion of monocytes
and neutrophils acquire characteristics of MDSC, it remains unclear which specific mechanisms are
responsible for such conversion. An abundance of immune suppressive mechanisms detected in MDSC
also raised the question, why accumulation of these cells in cancer, does not result in profound global
immune suppression of the host. This gap in our knowledge impedes progress toward targeting MDSC
function in order to increase the efficacy of immunotherapies. Our new preliminary data suggest that type
1 interferons (IFN1) signaling have an intrinsic regulatory role in preventing acquisition of the immune
suppressive potential by neutrophils and monocytes and in limiting suppressive activity of MDSC. All
IFN1 (including IFN-α and IFN-β) signal via binding to a surface receptor composed of two chains
(IFNAR1/2). Based on our preliminary data we hypothesize that IFN1 produced during inflammation or
cancer interferes with acquisition of immune suppressive activity by MDSC. During acute viral and
bacterial infections this mechanism prevents the development of immune suppressive activity by
neutrophils and monocytes, which otherwise would compromise immune responses. In cancer, however,
this mechanism is limited due to tumor-induced downregulation of IFNAR1. As a result, negative IFN1
signaling in MDSC is blocked and these cells can display potent suppressive activity that limits the effect
of cancer immunotherapy. Thus, targeting down-regulation of IFNAR1 in MDSC may have valuable
therapeutic effect. Overall goal of this proposal is to identify biological and biochemical mechanisms
negatively regulating immune suppressive activity of MDSC and to develop methods of their therapeutic
regulation.

## Key facts

- **NIH application ID:** 9830508
- **Project number:** 5R01CA216936-03
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Serge Y Fuchs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $547,478
- **Award type:** 5
- **Project period:** 2017-12-18 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830508

## Citation

> US National Institutes of Health, RePORTER application 9830508, Negative regulation of myeloid-derived suppressive cells in cancer (5R01CA216936-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9830508. Licensed CC0.

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