Microglia isolated from patients with glioma gain antitumor activities on poly (I:C) stimulation.
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.
INSERM U701, German Cancer Research Centre, INF 242, Germany.
Tim
T
Kees
Jennifer
J
Lohr
Johannes
J
Noack
Rodrigo
R
Mora
Georg
G
Gdynia
Grischa
G
Tödt
Aurélie
A
Ernst
Bernhard
B
Radlwimmer
Christine S
CS
Falk
Christel
C
Herold-Mende
Anne
A
Régnier-Vigouroux
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009361:Neoplasm Invasiveness; D011070:Poly I-C / Q000494:pharmacology*; D051196:Toll-Like Receptor 3 / Q000819:agonists*
D000970:Antineoplastic Agents; D051196:Toll-Like Receptor 3; D011070:Poly I-C