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Review

Decipher the Glioblastoma Microenvironment: The First Milestone for New Groundbreaking Therapeutic Strategies

1
Division of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
2
Anatomia Patologica 1, Department of Laboratory Medicine, Pisa University Hospital, 56126 Pisa, Italy
3
Division of Radiation Oncology, Department of Medical and Oncological Area, Pisa University Hospital, 56126 Pisa, Italy
4
Division of Neurosurgery, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
*
Author to whom correspondence should be addressed.
Co-Last authors.
Academic Editor: Gael Roue
Genes 2021, 12(3), 445; https://doi.org/10.3390/genes12030445
Received: 8 February 2021 / Revised: 12 March 2021 / Accepted: 17 March 2021 / Published: 20 March 2021
(This article belongs to the Special Issue Molecular Biomarkers in Solid Tumors)
Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite the combination of novel therapeutical approaches, it remains a deadly malignancy with an abysmal prognosis. GBM is a polymorphic tumour from both molecular and histological points of view. It consists of different malignant cells and various stromal cells, contributing to tumour initiation, progression, and treatment response. GBM’s microenvironment is multifaceted and is made up of soluble factors, extracellular matrix components, tissue-resident cell types (e.g., neurons, astrocytes, endothelial cells, pericytes, and fibroblasts) together with resident (e.g., microglia) or recruited (e.g., bone marrow-derived macrophages) immune cells. These latter constitute the so-called immune microenvironment, accounting for a substantial GBM’s tumour volume. Despite the abundance of immune cells, an intense state of tumour immunosuppression is promoted and developed; this represents the significant challenge for cancer cells’ immune-mediated destruction. Though literature data suggest that distinct GBM’s subtypes harbour differences in their microenvironment, its role in treatment response remains obscure. However, an in-depth investigation of GBM’s microenvironment may lead to novel therapeutic opportunities to improve patients’ outcomes. This review will elucidate the GBM’s microenvironment composition, highlighting the current state of the art in immunotherapy approaches. We will focus on novel strategies of active and passive immunotherapies, including vaccination, gene therapy, checkpoint blockade, and adoptive T-cell therapies. View Full-Text
Keywords: glioblastoma; tumour microenvironment; immunotherapy; cancer stem-cells glioblastoma; tumour microenvironment; immunotherapy; cancer stem-cells
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MDPI and ACS Style

Fanelli, G.N.; Grassini, D.; Ortenzi, V.; Pasqualetti, F.; Montemurro, N.; Perrini, P.; Naccarato, A.G.; Scatena, C. Decipher the Glioblastoma Microenvironment: The First Milestone for New Groundbreaking Therapeutic Strategies. Genes 2021, 12, 445. https://doi.org/10.3390/genes12030445

AMA Style

Fanelli GN, Grassini D, Ortenzi V, Pasqualetti F, Montemurro N, Perrini P, Naccarato AG, Scatena C. Decipher the Glioblastoma Microenvironment: The First Milestone for New Groundbreaking Therapeutic Strategies. Genes. 2021; 12(3):445. https://doi.org/10.3390/genes12030445

Chicago/Turabian Style

Fanelli, Giuseppe N., Dario Grassini, Valerio Ortenzi, Francesco Pasqualetti, Nicola Montemurro, Paolo Perrini, Antonio G. Naccarato, and Cristian Scatena. 2021. "Decipher the Glioblastoma Microenvironment: The First Milestone for New Groundbreaking Therapeutic Strategies" Genes 12, no. 3: 445. https://doi.org/10.3390/genes12030445

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