Journal Article

Microglia isolated from patients with glioma gain antitumor activities on poly (I:C) stimulation

Tim Kees, Jennifer Lohr, Johannes Noack, Rodrigo Mora, Georg Gdynia, Grischa Tödt, Aurélie Ernst, Bernhard Radlwimmer, Christine S. Falk, Christel Herold-Mende and Anne Régnier-Vigouroux

in Neuro-Oncology

Published on behalf of Society for Neuro-Oncology

Volume 14, issue 1, pages 64-78
Published in print January 2012 | ISSN: 1522-8517
Published online October 2011 | e-ISSN: 1523-5866 | DOI: https://dx.doi.org/10.1093/neuonc/nor182
Microglia isolated from patients with glioma gain antitumor activities on poly (I:C) stimulation

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The role of microglia, the brain-resident macrophages, in glioma biology is still a matter of debate. Clinical observations and in vitro studies in the mouse model indicate that microglia and macrophages that infiltrate the brain tumor tissue in high numbers play a tumor-supportive role. Here, we provide evidence that human microglia isolated from brain tumors indeed support tumor cell growth, migration, and invasion. However, after stimulation with the Toll-like receptor 3 agonist poly (I:C), microglia secrete factors that exerted toxic and suppressive effects on different glioblastoma cell lines, as assessed in cytotoxicity, migration, and tumor cell spheroid invasion assays. Remarkably, these effects were tumor-specific because the microglial factors impaired neither growth nor viability of astrocytes and neurons. Culture supernatants of tumor cells inhibited the poly (I:C) induction of this microglial M1-like, oncotoxic profile. Microglia stimulation before coculture with tumor cells circumvented the tumor-mediated suppression, as demonstrated by the ability to kill and phagocytose glioma cells. Our results show, for the first time to our knowledge, that human microglia exert tumor-supporting functions that are overridden by tumor-suppressing activities gained after poly (I:C) stimulation.

Keywords: antitumor response; glioma; human microglia; poly (I:C)

Journal Article.  6820 words.  Illustrated.

Subjects: Medical Oncology ; Neurology

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