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Review
. 2024 Sep 5;46(9):9881-9894.
doi: 10.3390/cimb46090588.

Glioblastoma Tumor Microenvironment: An Important Modulator for Tumoral Progression and Therapy Resistance

Ligia Gabriela Tataranu  1   2 , Serban Turliuc  3 , Amira Kamel  2 , Radu Eugen Rizea  1   2 , Anica Dricu  4 , Georgiana-Adeline Staicu  4 , Stefania Carina Baloi  4 , Silvia Mara Baez Rodriguez  2 , Andrada Ioana Maria Manole  2
Affiliations
Review

Glioblastoma Tumor Microenvironment: An Important Modulator for Tumoral Progression and Therapy Resistance

Ligia Gabriela Tataranu et al. Curr Issues Mol Biol. .

Abstract

The race to find an effective treatment for glioblastoma (GBM) remains a critical topic, because of its high aggressivity and impact on survival and the quality of life. Currently, due to GBM's high heterogeneity, the conventional treatment success rate and response to therapy are relatively low, with a median survival rate of less than 20 months. A new point of view can be provided by the comprehension of the tumor microenvironment (TME) in pursuance of the development of new therapeutic strategies to aim for a longer survival rate with an improved quality of life and longer disease-free interval (DFI). The main components of the GBM TME are represented by the extracellular matrix (ECM), glioma cells and glioma stem cells (GSCs), immune cells (microglia, macrophages, neutrophils, lymphocytes), neuronal cells, all of them having dynamic interactions and being able to influence the tumoral growth, progression, and drug resistance thus being a potential therapeutic target. This paper will review the latest research on the GBM TME and the potential therapeutic targets to form an up-to-date strategy.

Keywords: extracellular matrix; glioblastoma; molecular diagnostic; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Glioblastoma Tumor Microenvironment: The GBM TME is complex, with a series of unique features, interactions, and components—the ECM, with glycoproteins, proteoglycans, and glycosaminoglycans (e.g., HA), has an important role in creating a barrier between the GBM TME and the normal tissue, promoting invasiveness; the immune cells (GAMs, TANs, monocytes, tumor-infiltrating lymphocytes), neuronal cells, glial cells, and glioma stem cells; chemokines, hormones, enzymes, EVs, and cell-communicating factors like VEGF, EGFR, and mediators like glutamate, with all of them being involved in creating an hypoxic and immunosuppressive TME that promotes tumoral progression and therapy resistance. The blood–brain barrier is also important in modulating the GBM TME components and can limit tissue drug availability, playing an important role in therapy resistance.
Figure 2
Figure 2
The GBM TME is formed by a heterogeneous cell population represented by glioblastoma cells, macrophages, monocytes, microglia—TAMs, tumor-associated neutrophiles—TANs, dendritic cells, astrocytes, endothelial cells, myeloid-derived suppressor cells MDSCs, who are in a close connection, being linked together by mediators and chemoattraction processes.
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