CROSSTALK BETWEEN GLIOMA CELLS AND TUMOR ASSOCIATED-MACROPHAGES: MECHANISMS AND THERAPEUTIC STRATEGIES
type: CreativeWork
description: Macrophages are highly plastic cells, able to respond to several microenvironment signals acquiring distinct functional phenotypes. In Glioblastoma (GBM), the most common malignant brain tumor, tumor-associated-macrophages (TAMs) represent the major infiltrating immune cell populations and are key drivers of the local immunosuppression supporting tumor progression and the resistance to immunomodulating treatments. Mutations in enzymes isocitrate dehydrogenases (IDH) occur in GBM subsets, characterized by more favorable prognosis. Also, other molecular alterations and metabolic features, such as accumulation of the oncometabolite 2-hydroxyglutarate, are associated with IDH-mutations. Despite many therapeutic strategies, GBM recur in almost all patients and prognosis remain poor, the development of new therapeutic strategies is strongly needed. In the last decades, innovative engineered nanovectors bears a promise for GBM treatment: these multifunctionalized liposomes encapsulate drugs and are able to cross the blood brain barrier that will guarantee the localized release of candidate drugs to control neuroinflammation. The aim of the present study is to investigate the relevance of the cross-talk between macrophages and glioma cells, needed to overcome limitations of the current therapeutic approaches. Firstly, we analysed the interplay between macrophages and U87 glioma cells lines, harbouring wild-type or mutant IDH genes, through direct and indirect cocultures. Then we investigated the mechanisms underlying the macrophages-glioma cells’ crosstalk in hypoxia, a key aspect of the tumor microenvironment. In addition, in the context of nanovectors’ strategy, we set coculture models of macrophages and patient-derived GSCs to explore the potential of macrophages as target cells of encapsulated drugs for the rebalance of the glioma microenvironment. In our results, we showed that glioma-derived factors, released by U87 IDH1-WT and IDH-MUT, are able to polarize macrophage…
abstract: Macrophages are highly plastic cells, able to respond to several microenvironment signals acquiring distinct functional phenotypes. In Glioblastoma (GBM), the most common malignant brain tumor, tumor-associated-macrophages (TAMs) represent the major infiltrating immune cell populations and are key drivers of the local immunosuppression supporting tumor progression and the resistance to immunomodulating treatments. Mutations in enzymes isocitrate dehydrogenases (IDH) occur in GBM subsets, characterized by more favorable prognosis. Also, other molecular alterations and metabolic features, such as accumulation of the oncometabolite 2-hydroxyglutarate, are associated with IDH-mutations. Despite many therapeutic strategies, GBM recur in almost all patients and prognosis remain poor, the development of new therapeutic strategies is strongly needed. In the last decades, innovative engineered nanovectors bears a promise for GBM treatment: these multifunctionalized liposomes encapsulate drugs and are able to cross the blood brain barrier that will guarantee the localized release of candidate drugs to control neuroinflammation. The aim of the present study is to investigate the relevance of the cross-talk between macrophages and glioma cells, needed to overcome limitations of the current therapeutic approaches. Firstly, we analysed the interplay between macrophages and U87 glioma cells lines, harbouring wild-type or mutant IDH genes, through direct and indirect cocultures. Then we investigated the mechanisms underlying the macrophages-glioma cells’ crosstalk in hypoxia, a key aspect of the tumor microenvironment. In addition, in the context of nanovectors’ strategy, we set coculture models of macrophages and patient-derived GSCs to explore the potential of macrophages as target cells of encapsulated drugs for the rebalance of the glioma microenvironment. In our results, we showed that glioma-derived factors, released by U87 IDH1-WT and IDH-MUT, are able to polarize macrophage…
author: MAIELLI, ALESSANDRA
language: eng
keywords: Settore MED/06 - Oncologia Medica, Settore BIO/11 - Biologia Molecolare
date published: 2023-04-19
date modified: 2026-07-27T20:18:43Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/957829

PropertyValue
property ID: DOI
value: 10.13130/maielli-alessandra_phd2023-04-19