# Targeting macrophage reprogramming in glioblastoma

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $390,937

## Abstract

Project Summary
Glioblastoma is the most lethal form of primary brain cancer in adults with a median survival of approximately
14-16 months following diagnosis. In contrast to glioma cells, components of the tumor microenvironment (TME)
of glioblastoma are genetically stable and are considering as the promising therapeutic targets. Tumor-
associated macrophages (TAMs) are the most abundant cell population in the TME, which account for up to 50%
of total cells in the entire glioblastoma tumor mass. Macrophages exhibit a spectrum of functions that span from
an anti-tumor (known as M1) to a pro-tumor (known as M2) phenotype. TAMs are usually skewed toward a pro-
tumor phenotype in glioblastoma. Given the predominance of these cells in glioblastoma, therapeutic strategies
for their reprogramming to an anti-tumor phenotype is desirable. G protein-coupled receptors are a large family
of receptors that are prominent pharmacological targets in biomedicine. Our preliminary data shows that G
protein-coupled receptor 183 (GPR183) is highly expressed by TAMs in glioblastoma and may involve in TAM
pro-tumor phenotype polarization. In this proposal, we will investigate whether and how GPR183 contributes to
TAM pro-tumor phenotype polarization, reveal how such polarized TAMs promote tumor progression, and
develop potential therapeutic strategies targeting TAM reprogramming in glioblastoma. To achieve these goals,
we propose the following specific Aims: Aim 1. Clarify the role and underlying mechanism of GPR183 in TAM
reprogramming in glioblastoma; Aim 2. Determine how GPR183-regulated TAM reprogramming promotes
glioblastoma progression; and Aim 3. Basic to translational study: targeting TAM reprogramming using tumor
samples and models from glioblastoma patients. We propose to employ integrated strategies combining gain-
and loss-of-function approaches, in vitro and in vivo systems, as well as proteomic and transcriptomic analysis
to test each Aim. Together, this project will uncover novel mechanisms for TAM reprogramming and reveal new
immunotherapeutic strategies for glioblastoma.

## Key facts

- **NIH application ID:** 11126127
- **Project number:** 7R01NS127824-02
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Peiwen Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,937
- **Award type:** 7
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11126127

## Citation

> US National Institutes of Health, RePORTER application 11126127, Targeting macrophage reprogramming in glioblastoma (7R01NS127824-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11126127. Licensed CC0.

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