The glioblastoma (GBM) immune microenvironment is highly heterogeneous, and microglia may represent 30–70% of the entire tumor. However, the role of microglia and other specific immune populations is poorly characterized. Activation of mTOR signaling occurs in numerous human cancers and has roles in microglia-glioma cell interactions. We now show in human tumor specimens (42 patients), that 39% of tumor-associated microglial (TAM) cells express mTOR phosphorylated at Ser-2448; and similar mTOR activation is observed using a human microglia-glioma interaction paradigm. In addition, we confirm previous studies that microglia express urea and ARG1 (taken as M2 marker) in the presence of glioma cells, and this phenotype is down-regulated in the presence of a mTOR inhibitor. These results suggest that mTOR suppression in GBM patients might induce a reduction of the M2 phenotype expression in up to 40% of all TAMs. Since the M2 profile of microglial activation is believed to be associated with tumor progression, reductions in that phenotype may represent an additional anti-tumor mechanism of action of mTOR inhibitors, along with direct anti-proliferative activities.

Lisi, L., Ciotti, G. M. P., Chiavari, M., Pizzoferrato, M., Mangiola, A., Kalinin, S., Feinstein, D. L., Navarra, P., Phospho-mTOR expression in human glioblastoma microglia-macrophage cells, <<NEUROCHEMISTRY INTERNATIONAL>>, 2019; 129 (na): 104485-147797. [doi:10.1016/j.neuint.2019.104485] [http://hdl.handle.net/10807/147635]

Phospho-mTOR expression in human glioblastoma microglia-macrophage cells

Lisi, L.;Chiavari, M.;Pizzoferrato, M.;Navarra, P.
2019

Abstract

The glioblastoma (GBM) immune microenvironment is highly heterogeneous, and microglia may represent 30–70% of the entire tumor. However, the role of microglia and other specific immune populations is poorly characterized. Activation of mTOR signaling occurs in numerous human cancers and has roles in microglia-glioma cell interactions. We now show in human tumor specimens (42 patients), that 39% of tumor-associated microglial (TAM) cells express mTOR phosphorylated at Ser-2448; and similar mTOR activation is observed using a human microglia-glioma interaction paradigm. In addition, we confirm previous studies that microglia express urea and ARG1 (taken as M2 marker) in the presence of glioma cells, and this phenotype is down-regulated in the presence of a mTOR inhibitor. These results suggest that mTOR suppression in GBM patients might induce a reduction of the M2 phenotype expression in up to 40% of all TAMs. Since the M2 profile of microglial activation is believed to be associated with tumor progression, reductions in that phenotype may represent an additional anti-tumor mechanism of action of mTOR inhibitors, along with direct anti-proliferative activities.
Inglese
Lisi, L., Ciotti, G. M. P., Chiavari, M., Pizzoferrato, M., Mangiola, A., Kalinin, S., Feinstein, D. L., Navarra, P., Phospho-mTOR expression in human glioblastoma microglia-macrophage cells, <<NEUROCHEMISTRY INTERNATIONAL>>, 2019; 129 (na): 104485-147797. [doi:10.1016/j.neuint.2019.104485] [http://hdl.handle.net/10807/147635]
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