Λεπτομέρειες βιβλιογραφικής εγγραφής
| Τίτλος: |
Microglia Reprogramming in Glioblastoma: Stem Cell-Derived Factors as Emerging Immunomodulators. |
| Συγγραφείς: |
Amiri Z; Section of Pharmacology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy., Tremonti BF; Section of Pharmacology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy., Corsaro A; Section of Pharmacology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy., Pattarozzi A; Section of Pharmacology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy., Bajetto A; Section of Pharmacology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy., Barbieri F; Section of Pharmacology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy.; IRCCS Azienda Ospedaliera Metropolitana, Largo Rosanna Benzi 10, 16132 Genova, Italy., Thellung S; Section of Pharmacology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy.; IRCCS Azienda Ospedaliera Metropolitana, Largo Rosanna Benzi 10, 16132 Genova, Italy., Florio T; Section of Pharmacology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy.; IRCCS Azienda Ospedaliera Metropolitana, Largo Rosanna Benzi 10, 16132 Genova, Italy. |
| Πηγή: |
Cells [Cells] 2026 May 04; Vol. 15 (9). Date of Electronic Publication: 2026 May 04. |
| Τύπος έκδοσης: |
Journal Article; Review |
| Γλώσσα: |
English |
| Στοιχεία περιοδικού: |
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE |
| Imprint Name(s): |
Original Publication: Basel, Switzerland : MDPI |
| Ιατρικοί όροι (MeSH): |
Glioblastoma*/pathology , Glioblastoma*/immunology , Glioblastoma*/metabolism , Microglia*/metabolism , Microglia*/pathology , Brain Neoplasms*/pathology , Brain Neoplasms*/immunology , Immunologic Factors*/metabolism , Stem Cells*/metabolism , Cellular Reprogramming*, Extracellular Vesicles/metabolism ; Humans ; Animals ; Tumor Microenvironment ; Metabolic Reprogramming |
| Περίληψη: |
Glioblastoma (GBM) remains one of the most challenging forms of cancer to treat, despite that extensive molecular profiling is now available. Indeed, intratumoral cellular heterogeneity, receptor redundancy, and adaptive resistance through compensatory signaling limit the impact of targeted therapies. Moreover, immunotherapies also underperform: checkpoint blockade and vaccine strategies did not obtain consistent benefits in a low mutational burden, poorly immunogenic tumor microenvironment (TME) dominated by immunosuppressive myeloid cells. In this article, we provide evidence that tumor-associated macrophages (TAMs), a form of CNS resident microglia and infiltrating macrophage, derived from bone marrow, adopt a spatially and transcriptionally distinct, non-binary continuum, shaped by tumor-derived signals and niche constraints, allowing glioma cells to resist to immune and pharmaceutical therapeutics. Metabolic rewiring, including hypoxia-linked glycolytic pressure, lactate signaling, and lipid-associated programs, determine immunosuppressive outputs and restrict plasticity, while epigenetic imprinting (DNA methylation, histone modifications, and chromatin regulators) stabilizes these programs and limits access to inflammatory loci. We discuss how stem cell secretome, and extracellular vesicles (EVs) and their cargo may act as tunable autocrine/paracrine inputs that may bias microglial regulatory control. Finally, we highlight major translational confounders, including EV operational definitions, blood-brain barrier (BBB) permeability and regional exposure, inconsistent dosing units, mixed myeloid compartments, and manufacturing dependent variability. Therefore, an exposure-aware framework that integrates product identity, delivery evidence, state-sensitive potency assays, and functional endpoints would be highly desirable. |
| Grant Information: |
MNESYS (PE0000006) NEXTGENERATIONEU (NGEU) National Recovery and Resilience Plan, Ministry of University Research (MUR), Italy; Hybrid Hub (H2UB): Cellular and computational models, micro- and nanotechnologies for the personalisation of innovative therapies" (T4-AN-10) Development and Cohesion Plan of the Italian Ministry of Health |
| Contributed Indexing: |
Keywords: epigenetic reprogramming; extracellular vesicles; glioblastoma; immunosuppression; metabolic reprogramming; microglia reprogramming; potency assays; stem cell secretome; tumor microenvironment; tumor-associated macrophages |
| Substance Nomenclature: |
0 (Immunologic Factors) |
| Entry Date(s): |
Date Created: 20260513 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: |
20260717 |
| PubMed Central ID: |
PMC13163103 |
| DOI: |
10.3390/cells15090840 |
| PMID: |
42121941 |
| Βάση Δεδομένων: |
MEDLINE |