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Review
. 2022 May 31;12(6):718.
doi: 10.3390/brainsci12060718.

Glioma-Associated Microglia Characterization in the Glioblastoma Microenvironment through a 'Seed-and Soil' Approach: A Systematic Review

Grazia Menna  1 , Pier Paolo Mattogno  1 , Carlo Maria Donzelli  1 , Lucia Lisi  2 , Alessandro Olivi  1 , Giuseppe Maria Della Pepa  1
Affiliations
Review

Glioma-Associated Microglia Characterization in the Glioblastoma Microenvironment through a 'Seed-and Soil' Approach: A Systematic Review

Grazia Menna et al. Brain Sci. .

Abstract

Background and aim: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A "seed and soil" approach has been recently introduced to describe the glioblastoma (GBM) landscape: tumor microenvironments act as fertile "soil" and interact with the "seed" (glial and stem cells compartment). In the following article, we provide a systematic review of the current evidence pertaining to the characterization of glioma-associated macrophages and microglia (GAMs) and microglia and macrophage cells in the glioma tumor microenvironment (TME). Methods: An online literature search was launched on PubMed Medline and Scopus using the following research string: "((Glioma associated macrophages OR GAM OR Microglia) AND (glioblastoma tumor microenvironment OR TME))". The last search for articles pertinent to the topic was conducted in February 2022. Results: The search of the literature yielded a total of 349 results. A total of 235 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 58 articles were included in the review. The reviewed papers were further divided into three categories based on their focus: (1) Microglia maintenance of immunological homeostasis and protection against autoimmunity; (2) Microglia crosstalk with dedifferentiated and stem-like glioblastoma cells; (3) Microglia migratory behavior and its activation pattern. Conclusions: Aggressive growth, inevitable recurrence, and scarce response to immunotherapies are driving the necessity to focus on the GBM TME from a different perspective to possibly disentangle its role as a fertile 'soil' for tumor progression and identify within it feasible therapeutic targets. Against this background, our systematic review confirmed microglia to play a paramount role in promoting GBM progression and relapse after treatments. The correct and extensive understanding of microglia-glioma crosstalk could help in understanding the physiopathology of this complex disease, possibly opening scenarios for improvement of treatments.

Keywords: PD-L1; glioblastoma; glioma-associated microglia; immunological homeostasis; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Prisma diagram showing the research strategy and selection of papers included.
Figure 2
Figure 2
Schematic representation of multiple roles of microglia in Glioblastoma development, pathogenesis and relapse according a ‘seed and soil’ aproach.
See this image and copyright information in PMC

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