# Therapeutic targeting MDSC-mediated immune suppression in cancer

> **NIH NIH R01** · WISTAR INSTITUTE · 2022 · $714,368

## Abstract

Project Summary
The prominent change in the myeloid compartment in cancer is the expansion of pathologically activated
immature myeloid cells with the potent ability to suppress immune responses – myeloid-derived suppressor cells
(MDSC). In tumor-bearing mice, the total population of MDSC consists of three groups of cells: the most
abundant (>75%) immature, pathologically activated neutrophils (PMN-MDSC); less abundant (<20%)
population of pathologically activated monocytes (M-MDSC); and small (<5%) population of early myeloid
precursors. In the tumor microenvironment MDSC are more immunosuppressive than in peripheral lymphoid
organ. However, the mechanism of this phenomenon remains rather elusive. The gaps in our knowledge is in
understanding the mechanisms regulating the function of MDSC in tumors and specific requirements for their
targeting. In this proposal we will test the hypothesis that there are distinct populations of MDSC in tumors. These
populations can be defined by specific markers and most importantly, have different sensitivity to ferroptotic cell
death which determines their functional activity. We will test the concept that targeting ferroptosis in PMN-MDSC
in cancer may have functional consequences for immune responses. The goal of this project is to uncover the
mechanisms regulating myeloid cell function in tumors and to develop novel approaches to the regulation of
immune responses in cancer.
We propose the following Specific Aims: (1) To identify the mechanism of ferroptosis-mediated immune
suppression induced by PMN-MDSC in tumors; and (2) To investigate therapeutic potential of targeting
ferroptosis in PMN-MDSC.

## Key facts

- **NIH application ID:** 10340589
- **Project number:** 1R01CA266342-01
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Valerian E Kagan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $714,368
- **Award type:** 1
- **Project period:** 2021-12-13 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10340589

## Citation

> US National Institutes of Health, RePORTER application 10340589, Therapeutic targeting MDSC-mediated immune suppression in cancer (1R01CA266342-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10340589. Licensed CC0.

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