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Microglia-Derived Microvesicles Affect Microglia Phenotype in Glioma.

Alfonso Grimaldi1, Carmela Serpe2, Giuseppina Chece2

  • 1Center for Life Nanoscience, Istituto Italiano di Tecnologia@Sapienza, Rome, Italy.

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|March 12, 2019
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Summary

Microglia-derived extracellular vesicles (EVs) can reprogram tumor-associated myeloid cells in brain tumors. This transfer of information reduces tumor size and promotes brain homeostasis recovery.

Keywords:
brain tumorsextracellular vesiclesgliomamicrogliatumor associated myeloid cells

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Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Extracellular vesicles (EVs), including microvesicles (MV) and exosomes (Exo), mediate intercellular communication by transferring proteins, lipids, and nucleic acids.
  • In the nervous system, EVs are crucial for neuron-glial cross-talk, maintaining brain homeostasis and implicated in central nervous system (CNS) diseases when dysfunctional.

Purpose of the Study:

  • To investigate the potential of microglia-derived EVs to transfer a protective phenotype to dysfunctional microglia within a brain tumor microenvironment.
  • To assess the therapeutic efficacy of microvesicles in modulating tumor-associated myeloid cells and impacting glioma progression.

Main Methods:

  • Isolation of microvesicles (MV) from microglia stimulated with LPS/IFNγ.
  • Intracerebral injection of isolated MVs into glioma-bearing mice.
  • Analysis of tumor-associated myeloid cell (TAM) phenotype.
  • Assessment of tumor size, neuronal death, and glioma invasion.

Main Results:

  • Brain injection of microglia-derived MVs induced a phenotype switch in tumor-associated myeloid cells (TAMs).
  • A significant reduction in tumor size was observed in MV-treated glioma-bearing mice.
  • EV cargo, containing upregulated inflammation-related gene transcripts, modified microglial gene expression, reduced neuronal death, and inhibited glioma invasion.

Conclusions:

  • Microglia-derived MVs can serve as a therapeutic tool to transfer protective information to dysfunctional microglia in the context of brain tumors.
  • This EV-mediated intercellular communication promotes the recovery of brain homeostasis by modulating the tumor microenvironment and inhibiting glioma progression.