The Interplay between Glioblastoma and Its Microenvironment

Abstract

GBM is the most common primary brain tumor in adults, and the aggressive nature of this tumor contributes to its extremely poor prognosis. Over the years, the heterogeneous and adaptive nature of GBM has been highlighted as a major contributor to the poor efficacy of many treatments including various immunotherapies. The major challenge lies in understanding and manipulating the complex interplay among the different components within the tumor microenvironment (TME). This interplay varies not only by the type of cells interacting but also by their spatial distribution with the TME. This review highlights the various immune and non-immune components of the tumor microenvironment and their consequences f the efficacy of immunotherapies. Understanding the independent and interdependent aspects of the various sub-populations encapsulated by the immune and non-immune components will allow for more targeted therapies. Meanwhile, understanding how the TME creates and responds to different environmental pressures such as hypoxia may allow for other multimodal approaches in the treatment of GBM. Ultimately, a better understanding of the GBM TME will aid in the development and advancement of more effective treatments and in improving patient outcomes.

Pyroptosis-related prognosis model, immunocyte infiltration characterization, and competing endogenous RNA network of glioblastoma

“…The Tumor microenvironment (TME) is the site of tumor cell growth and development. It is composed of stromal cells, signaling molecules, immune cells and extracellular matrix (ECM) [ 11 ]. TME plays an important role in the progression and treatment resistance of GBM [ 12 ].…”

Dialogue among Lymphocytes and Microglia in Glioblastoma Microenvironment

“…The genetic complexity shown in GBM involves several genetic and epigenetic modifications that result in the loss of tumor suppressor gene function (CDKN2A/B and PTEN) or the activation of oncogenic pathways (CDK4, p21–RAS, and MDM2) [ 22 , 23 , 24 ]. This genetic heterogeneity is accompanied by a high diversity in the cell populations forming the GBM microenvironment (GME), such as resident and peripheral immune cells, endothelial cells, mesenchymal cells, and glioma stem cells (GSCs) [ 25 ]. GSCs are characterized by the ability to differentiate into different cell lineages to reconstitute the tumor mass.…”

Small Molecules and Immunotherapy Agents for Enhancing Radiotherapy in Glioblastoma

“…Key studies have suggested the TME in GBM plays a key role in the development of tumor hypoxia [ 48 ]. The TME is composed of stromal cells, signaling molecules, immune cells, and the surrounding extracellular matrix [ 49 ]. This complex matrix of cells creates pockets of hypoxia and acidosis via “microvascular hyperplasia” where rapidly dividing endothelial cells form microaggregates of sprouting vessels [ 50 ].…”