# Role of IRF2BP2 in Tumor Immune Evasion

> **NIH NIH F31** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $51,752

## Abstract

PROJECT ABSTRACT
Understanding the tumor microenvironment (TME) and the prognostic relevance of the cells contributing to it is
vital for developing novel treatments for medulloblastoma (MB), the most common malignant pediatric brain
tumor. Immune resistance in a murine model of MB (MM1) is associated with enhanced tumor expression of the
immune checkpoint programmed death ligand-1 (PD-L1) in response to anti-tumor cytokine interferon-gamma
(IFNγ) signaling. Disruption of this pathway via knockdown of cyclin dependent kinase 5 (CDK5), an essential
transducer of the IFNγ signal, leads to an inflammatory TME phenotype and enhanced tumor rejection in vivo.
IFNγ-induced PD-L1 gene expression is thought to be regulated at the promoter level by competition between
the transcriptional activator IRF1 and repressor IRF2. IFNγ-Cdk5 signaling decreases IRF2 expression and is
associated with hypo-phosphorylation of its co-repressor IRF2BP2, driving IRF1-mediated transcriptional
activation.
IRF2BP2 has emerged as a vital transcriptional co-factor in multiple cell types, with roles in the regulation of
apoptosis, cell cycling, and inflammation. However, its function in cancer is poorly defined. We hypothesize that
formation of the IRF2/IRF2BP2 co-repressor normally attenuates PD-L1 transcription, and that inhibition of this
complex by IFNγ-Cdk5 signaling unleashes PD-L1 expression and results in immune evasion. This project aims
to assess the function of the IRF2/IRF2BP2 complex at the PD-L1 promoter level during basal and IFNγ-
stimulated conditions in MB, with complementary studies on how perturbations in this tumor-intrinsic signaling
pathway leads to shifts in the TME composition in vivo. Aim 1 will characterize the role of IRF2BP2 in mediating
the function of interferon-sensitive response elements (ISRE)-containing gene promoters. Aim 2 will assess the
effect of IRF2BP2 on tumor growth and immune infiltration in vivo. Success in this effort will enable an in-depth
understanding of the tumor-intrinsic regulation of immune sensitivities in MB, thereby facilitating rational targeted
immunotherapeutic approach development in the future against MB and possibly other cancers.

## Key facts

- **NIH application ID:** 10410406
- **Project number:** 5F31CA254259-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** muta abiff
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2021-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10410406

## Citation

> US National Institutes of Health, RePORTER application 10410406, Role of IRF2BP2 in Tumor Immune Evasion (5F31CA254259-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10410406. Licensed CC0.

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