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Environmental stimuli shape microglial plasticity in glioma.

eLife | 2017

In glioma, microglia and infiltrating macrophages are exposed to factors that force them to produce cytokines and chemokines, which contribute to tumor growth and to maintaining a pro-tumorigenic, immunosuppressed microenvironment. We demonstrate that housing glioma-bearing mice in enriched environment (EE) reverts the immunosuppressive phenotype of infiltrating myeloid cells, by modulating inflammatory gene expression. Under these conditions, the branching and patrolling activity of myeloid cells is increased, and their phagocytic activity is promoted. Modulation of gene expression depends on interferon-(IFN)-γ produced by natural killer (NK) cells. This modulation disappears in mice depleted of NK cells or lacking IFN-γ, and was mimicked by exogenous interleukin-15 (IL-15). Further, we describe a key role for brain-derived neurotrophic factor (BDNF) that is produced in the brain of mice housed in EE, in mediating the expression of IL-15 in CD11b+ cells. These data define novel mechanisms linking environmental cues to the acquisition of a pro-inflammatory, anti-tumor microenvironment in mouse brain.

Pubmed ID: 29286001 RIS Download

Associated grants

  • Agency: Associazione Italiana per la Ricerca sul Cancro, International
    Id: AIRC2015 IG16699
  • Agency: Ministero dell'Istruzione, dell'Università e della Ricerca, International
    Id: PRIN 2015
  • Agency: CRCHU, International
    Id: Starting Grant
  • Agency: European Commission, International
    Id: Euronanomed2: Nanoglio
  • Agency: Associazione Italiana per la Ricerca sul Cancro, International
    Id: AIRC2014 IG16014

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