# Role of NF-κB c-Rel in regulating Natural Killer cell anti-tumor functions

> **NIH NIH F31** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $47,355

## Abstract

Project Summary/Abstract
The immune system serves as a host-defense mechanism against invading pathogens and
transformed cells through an intricate network of signaling molecules and specialized cells.
Natural Killer (NK) cells are cytotoxic lymphocytes that kill virus-infected and cancer cells. They
are an integral component of tumor-immune surveillance. However, Natural Killer cells from
cancer patients are rendered dysfunctional1-10. Finding key factors that regulate NK cell cytotoxic
function is vital to understand the mechanistic alterations leading into NK cell dysfunction in
cancer. Various studies show that NK cell cytotoxicity can be mediated by cytokines including: IL-
2, GM-CSF, IL-15, IL-21, and TGF-β11-20, all of which are regulated by NF-κB c-Rel21-23. NF-κB c-
Rel is a transcription factor that is constitutively expressed in myeloid and lymphocytic lineages24.
Although c-Rel has been reported to promote T cell proliferation and cytokine production24-27, the
role of c-Rel in NK cells remains unknown. Preliminary studies utilizing purified murine WT and c-
Rel-/- NK cells, show that deficiency in c-Rel expression results in reduced perforin expression and
impaired anti-tumor function in murine NK cells. Similarly, inhibition of c-Rel with specific small
molecule inhibitor, lead to decreased perforin expression and impaired anti-tumor cytotoxicity of
human NK cells. We therefore seek to define the role of c-Rel in regulating mouse and human
NK cell anti-tumor cytotoxic activity. The first aim will define the role of c-Rel in regulating NK cell
cytotoxic function. The second aim will investigate the mechanism by which c-Rel regulates NK
cells ability to kill tumor cells. Completion of these aims will define the mechanism-driven c-Rel
regulation of NK cell cytotoxic function.

## Key facts

- **NIH application ID:** 10180916
- **Project number:** 5F31CA232648-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Yorleny M Vicioso
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $47,355
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180916

## Citation

> US National Institutes of Health, RePORTER application 10180916, Role of NF-κB c-Rel in regulating Natural Killer cell anti-tumor functions (5F31CA232648-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10180916. Licensed CC0.

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