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Updated: Jul 29, 2025
Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
Macrophages in Recurrent Glioblastoma as a Prognostic Factor in the Synergistic System of the Tumor Microenvironment
Nicola Montemurro1, Bhavya Pahwa2, Anish Tayal2
1Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana (AOUP), University of Pisa, 56100 Pisa, Italy.
Abstract:
Glioblastoma (GBM) is a common and highly malignant primary tumor of the central nervous system in adults. Ever more recent papers are focusing on understanding the role of the tumor microenvironment (TME) in affecting tumorigenesis and the subsequent prognosis. We assessed the impact of macrophages in the TME on the prognosis in patients with recurrent GBM. A PubMed, MEDLINE and Scopus review was conducted to identify all studies dealing with macrophages in the GBM microenvironment from January 2016 to December 2022. Glioma-associated macrophages (GAMs) act critically in enhancing tumor progression and can alter drug resistance, promoting resistance to radiotherapy and establishing an immunosuppressive environment. M1 macrophages are characterized by increased secretion of proinflammatory cytokines, such as IL-1ß, tumor necrosis factor (TNF), IL-27, matrix metalloproteinase (MMPs), CCL2, and VEGF (vascular endothelial growth factor), IGF1, that can lead to the destruction of the tissue. In contrast, M2 is supposed to participate in immunosuppression and tumor progression, which is formed after being exposed to the macrophage M-CSF, IL-10, IL-35 and the transforming growth factor-ß (TGF-β). Because there is currently no standard of care in recurrent GBM, novel identified targeted therapies based on the complex signaling and interactions between the glioma stem cells (GSCs) and the TME, especially resident microglia and bone-marrow-derived macrophages, may be helpful in improving the overall survival of these patients in the near future.
Insights
Macrophages in the tumor microenvironment significantly impact glioblastoma (GBM) progression and treatment resistance. Targeting these glioma-associated macrophages (GAMs) offers potential for improved survival in recurrent GBM patients.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Biology
Background:
- Glioblastoma (GBM) is a highly malignant brain tumor.
- The tumor microenvironment (TME) plays a crucial role in GBM tumorigenesis and patient prognosis.
- Macrophages within the TME are key players influencing GBM progression.
Purpose of the Study:
- To assess the impact of macrophages in the TME on the prognosis of patients with recurrent GBM.
- To review the literature on macrophages within the GBM microenvironment from January 2016 to December 2022.
Main Methods:
- A comprehensive literature review was conducted using PubMed, MEDLINE, and Scopus databases.
- Studies focusing on macrophages in the GBM microenvironment published between January 2016 and December 2022 were identified.
Main Results:
- Glioma-associated macrophages (GAMs) promote GBM progression, drug resistance, and radiotherapy resistance.
- GAMs create an immunosuppressive environment within the TME.
- M1 macrophages secrete pro-inflammatory cytokines, while M2 macrophages are linked to immunosuppression and tumor progression.
Conclusions:
- Targeted therapies focusing on the interactions between glioma stem cells (GSCs) and the TME, particularly macrophages, may improve survival in recurrent GBM.
- Further research into macrophage-specific therapies is warranted due to the lack of a standard of care for recurrent GBM.
