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Updated: Apr 30, 2026
Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
Semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia
Ian S Miller1, Sebastien Didier1, David W Murray1
1Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research at North Shore-LIJ, Manhasset, New York, United States of America.
Abstract:
Glioblastoma is the most malignant and lethal form of astrocytoma, with patients having a median survival time of approximately 15 months with current therapeutic modalities. It is therefore important to identify novel therapeutics. There is mounting evidence that microglia (specialized brain-resident macrophages) play a significant role in the development and progression of glioblastoma tumors. In this paper we show that microglia, in addition to stimulating glioblastoma cell invasion, also promote glioblastoma cell proliferation and resistance to ionizing radiation in vitro. We found that semapimod, a drug that selectively interferes with the function of macrophages and microglia, potently inhibits microglia-stimulated GL261 invasion, without affecting serum-stimulated glioblastoma cell invasion. Semapimod also inhibits microglia-stimulated resistance of glioblastoma cells to radiation, but has no significant effect on microglia-stimulated glioblastoma cell proliferation. We also found that intracranially administered semapimod strongly increases the survival of GL261 tumor-bearing animals in combination with radiation, but has no significant benefit in the absence of radiation. In conclusion, our observations indicate that semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia and/or infiltrating macrophages.
Insights
Semapimod targets microglia to enhance glioblastoma treatment. This drug, combined with radiation, significantly improves survival in preclinical models by sensitizing tumors.
Area of Science:
- Neuro-oncology
- Immunology
- Pharmacology
Background:
- Glioblastoma is a lethal brain cancer with poor prognosis.
- Microglia, brain-resident macrophages, significantly influence glioblastoma progression.
- Novel therapeutics targeting the tumor microenvironment are crucial.
Purpose of the Study:
- To investigate the role of microglia in glioblastoma growth and radiation resistance.
- To evaluate the efficacy of semapimod, a macrophage/microglia inhibitor, in glioblastoma models.
- To determine if semapimod sensitizes glioblastoma to ionizing radiation.
Main Methods:
- In vitro studies assessing microglia-stimulated glioblastoma cell invasion, proliferation, and radiation resistance.
- Treatment of GL261 glioblastoma cells with semapimod and/or ionizing radiation.
- In vivo studies evaluating the effect of semapimod and radiation on tumor-bearing animal survival.
Main Results:
- Microglia promote glioblastoma cell invasion, proliferation, and radiation resistance in vitro.
- Semapimod inhibited microglia-stimulated invasion and radiation resistance, but not proliferation.
- Intracranial semapimod combined with radiation significantly increased survival in GL261 tumor-bearing mice.
Conclusions:
- Semapimod targets microglia and/or infiltrating macrophages to sensitize glioblastoma to ionizing radiation.
- Targeting the microglia-mediated tumor microenvironment represents a promising therapeutic strategy for glioblastoma.
- Combination therapy of semapimod and radiation shows significant survival benefit in preclinical glioblastoma models.
