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Updated: May 14, 2026
An Orthotopic Sciatic Nerve Xenograft for Neurofibromatosis Type 1 Neurofibromas
Published on: October 10, 2025
Reduced microglial CX3CR1 expression delays neurofibromatosis-1 glioma formation
Winnie W Pong1, Samantha B Higer, Scott M Gianino
1Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Abstract:
Although traditional models of carcinogenesis have largely focused on neoplastic cells, converging data have revealed the importance of non-neoplastic stromal cells in influencing tumor growth and progression. Leveraging a genetically engineered mouse model of neurofibromatosis type 1 (NF1)-associated optic glioma, we now demonstrate that stromal microglia express the CX3CR1 chemokine receptor, such that reduced CX3CR1 expression decreases optic nerve microglia. Moreover, genetic reduction of Cx3cr1 expression in Nf1 optic glioma mice delays optic glioma formation. Coupled with previous findings demonstrating that microglia maintain optic glioma growth, these new findings provide a strong preclinical rationale for the development of future stroma-directed glioma therapies in children.
Insights
Stromal microglia, crucial for tumor growth, express CX3CR1. Reducing this receptor in neurofibromatosis type 1 (NF1)-associated optic gliomas delays tumor formation, suggesting new stroma-directed therapies.
Area of Science:
- Oncology
- Neuroscience
- Immunology
Background:
- Traditional cancer models focus on neoplastic cells.
- Emerging evidence highlights the role of non-neoplastic stromal cells in tumor progression.
- Stromal cells, including microglia, significantly influence tumor microenvironment and growth.
Purpose of the Study:
- To investigate the role of stromal microglia and CX3CR1 in neurofibromatosis type 1 (NF1)-associated optic glioma.
- To determine if targeting CX3CR1 can impact optic glioma development and growth.
Main Methods:
- Utilized a genetically engineered mouse model of NF1-associated optic glioma.
- Assessed CX3CR1 chemokine receptor expression in stromal microglia.
- Genetically reduced Cx3cr1 expression in Nf1 optic glioma mice to evaluate its effect on tumor formation.
Main Results:
- Stromal microglia in NF1 optic gliomas express the CX3CR1 receptor.
- Reduced CX3CR1 expression led to decreased optic nerve microglia.
- Genetic reduction of Cx3cr1 expression significantly delayed optic glioma formation in Nf1 mice.
Conclusions:
- Stromal microglia play a critical role in the initiation and progression of NF1-associated optic gliomas.
- CX3CR1 signaling in microglia is a key factor in optic glioma development.
- These findings support the development of stroma-directed therapies targeting microglia for pediatric gliomas.
