# The c-Rel Checkpoint for Immunosuppression and Immunotherapy

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $508,853

## Abstract

The primary objectives of this research project are to characterize a new immune checkpoint and
to develop a new immunotherapeutic strategy to treat cancer. Immunotherapy that targets
lymphoid cell checkpoints holds great promise for curing cancer. However, a majority of cancer
patients do not respond to this form of therapy. In addition to lymphoid cells, myeloid cells play
essential roles in controlling immunity to cancer. Whether myeloid checkpoints exist that can be
targeted to treat cancer is not well established. Myeloid-derived suppressor cells (MDSCs) are a
newly identified population of leukocytes important for cancer. Depletion of MDSCs leads to
markedly enhanced anti-tumor immunity in mice, and may be crucial for the success of cancer
immunotherapy in humans. Despite their significance in cancer, MDSCs remain to be the least
understood subset of myeloid cells. It is unclear what transcriptional program specifies MDSC
differentiation; it is unknown what pharmaceutical approach can be used to target MDSCs for the
treatment of cancer. This grant application is inspired by our recent discovery that the transcription
factor c-Rel is required for both human and murine MDSC development and/or function, and that
c-Rel inhibitors are effective for treating cancer in mice. The goals of this project are to (i) elucidate
the mechanisms through which c-Rel regulates murine and human MDSCs, and (ii) establish the
efficacy and the mechanisms of action of our c-Rel inhibitors for the treatment of cancer.

## Key facts

- **NIH application ID:** 10102203
- **Project number:** 5R01AI152195-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** WARREN S PEAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $508,853
- **Award type:** 5
- **Project period:** 2020-02-11 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102203

## Citation

> US National Institutes of Health, RePORTER application 10102203, The c-Rel Checkpoint for Immunosuppression and Immunotherapy (5R01AI152195-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10102203. Licensed CC0.

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