Microglia promote glioblastoma via mTOR-mediated immunosuppression of the tumour microenvironment.

Details

Serval ID
serval:BIB_FFF9B15DBC96
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Microglia promote glioblastoma via mTOR-mediated immunosuppression of the tumour microenvironment.
Journal
The EMBO journal
Author(s)
Dumas A.A., Pomella N., Rosser G., Guglielmi L., Vinel C., Millner T.O., Rees J., Aley N., Sheer D., Wei J., Marisetty A., Heimberger A.B., Bowman R.L., Brandner S., Joyce J.A., Marino S.
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Publication state
Published
Issued date
03/08/2020
Peer-reviewed
Oui
Volume
39
Number
15
Pages
e103790
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Tumour-associated microglia/macrophages (TAM) are the most numerous non-neoplastic populations in the tumour microenvironment in glioblastoma multiforme (GBM), the most common malignant brain tumour in adulthood. The mTOR pathway, an important regulator of cell survival/proliferation, is upregulated in GBM, but little is known about the potential role of this pathway in TAM. Here, we show that GBM-initiating cells induce mTOR signalling in the microglia but not bone marrow-derived macrophages in both in vitro and in vivo GBM mouse models. mTOR-dependent regulation of STAT3 and NF-κB activity promotes an immunosuppressive microglial phenotype. This hinders effector T-cell infiltration, proliferation and immune reactivity, thereby contributing to tumour immune evasion and promoting tumour growth in mouse models. The translational value of our results is demonstrated in whole transcriptome datasets of human GBM and in a novel in vitro model, whereby expanded-potential stem cells (EPSC)-derived microglia-like cells are conditioned by syngeneic patient-derived GBM-initiating cells. These results raise the possibility that microglia could be the primary target of mTOR inhibition, rather than the intrinsic tumour cells in GBM.
Keywords
TAM, mTOR, T cells, glioblastoma, microglia, TAM, mTOR
Pubmed
Web of science
Open Access
Yes
Create date
03/07/2020 18:40
Last modification date
23/10/2020 5:23
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