Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice

Stefano Garofalo, Giuseppina D’Alessandro, Giuseppina Chece, Frederic Brau, Laura Maggi, Alessandro Rosa, Alessandra Porzia, Fabrizio Mainiero, Vincenzo Esposito, Clotilde Lauro, Giorgia Benigni, Giovanni Bernardini, Angela Santoni and Cristina Limatola ()
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Stefano Garofalo: Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University
Giuseppina D’Alessandro: Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University
Giuseppina Chece: Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University
Frederic Brau: Université Nice-Sophia Antipolis, IPMC CNRS-UMR
Laura Maggi: Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University
Alessandro Rosa: Sapienza University
Alessandra Porzia: Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University
Fabrizio Mainiero: Sapienza University
Vincenzo Esposito: IRCCS Neuromed
Clotilde Lauro: Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University
Giorgia Benigni: Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University
Giovanni Bernardini: Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University
Angela Santoni: Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University
Cristina Limatola: Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract Mice exposed to standard (SE) or enriched environment (EE) were transplanted with murine or human glioma cells and differences in tumour development were evaluated. We report that EE exposure affects: (i) tumour size, increasing mice survival; (ii) glioma establishment, proliferation and invasion; (iii) microglia/macrophage (M/Mφ) activation; (iv) natural killer (NK) cell infiltration and activation; and (v) cerebral levels of IL-15 and BDNF. Direct infusion of IL-15 or BDNF in the brain of mice transplanted with glioma significantly reduces tumour growth. We demonstrate that brain infusion of IL-15 increases the frequency of NK cell infiltrating the tumour and that NK cell depletion reduces the efficacy of EE and IL-15 on tumour size and of EE on mice survival. BDNF infusion reduces M/Mφ infiltration and CD68 immunoreactivity in tumour mass and reduces glioma migration inhibiting the small G protein RhoA through the truncated TrkB.T1 receptor. These results suggest alternative approaches for glioma treatment.

Date: 2015
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DOI: 10.1038/ncomms7623

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