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Updated: Jan 22, 2026
Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
Microglia and macrophages in human glioblastomas: A morphological and immunohistochemical study
Magnus Kvisten1, Vilde E Mikkelsen1, Anne Line Stensjøen2
1Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, NO-7491 Trondheim, Norway.
Abstract:
Glioblastomas (GBMs), a type of highly malignant brain tumour, contain various macrophages/microglia that are known as tumour-associated macrophages (TAMs). These TAMs have various roles in tumour biology. Histopathological aspects of TAMs and associations with tumour growth assessed by magnetic resonance imaging (MRI) are poorly described. In the present study, 16 patients that had sufficient tumour tissue and histological hallmarks were examined. The tumours were classified as either slow- (n=7) or fast-growing (n=9) based on the segmented tumour volumes from MRI scans taken at diagnosis and preoperatively. Using cluster of differentiation (CD)68 and ionized calcium-binding adaptor molecule 1 (Iba1) antibodies, the number, morphology, localization and distribution of TAMs in the GBM tissue were studied. TAMs were significantly more immunoreactive for anti-Iba1 (TAMsIba1) compared with anti-CD68 (TAMsCD68; P<0.001). In central tumour areas and around vessels in the infiltration zone there were more TAMsCD68 in slow-growing tumours (P=0.003 and P=0.025, respectively). Central tumour areas contained more TAMs compared with the infiltration zone (P=0.001 for TAMsCD68 and P<0.001 for TAMsIba1). The majority of TAMs exhibited a ramified phenotype in the infiltration zone, whereas central TAMs were mostly amoeboid. TAMs were present in high numbers in most regions of the tumour, whereas there were few in necrotic areas. In conclusion, the present study demonstrated and confirmed that the high numbers of TAMs in GBMs assume a range of morphologies consistent with various activation states, and that slow-growing GBMs seem to contain a TAM-population different to their fast-growing counterparts.
Insights
Tumor-associated macrophages (TAMs) in glioblastoma (GBM) show varied morphologies and distributions. Slow-growing GBMs exhibit distinct TAM populations compared to fast-growing ones, impacting tumor biology.
Area of Science:
- Neuro-oncology
- Immunology
- Pathology
Background:
- Glioblastomas (GBMs) are aggressive brain tumors characterized by tumor-associated macrophages (TAMs).
- The roles of TAMs in GBM biology and their histopathological features related to tumor growth are not well understood.
- Magnetic resonance imaging (MRI) is used to assess tumor volume and growth rates.
Purpose of the Study:
- To investigate the histopathological characteristics of TAMs in GBM.
- To correlate TAM morphology, distribution, and density with GBM growth rates assessed by MRI.
- To explore potential differences in TAM populations between slow-growing and fast-growing GBMs.
Main Methods:
- Analysis of GBM tissue from 16 patients with sufficient histological material.
- Classification of tumors into slow-growing (n=7) and fast-growing (n=9) based on MRI-derived segmented tumor volumes.
- Immunohistochemical staining using CD68 and Iba1 antibodies to study TAMs.
- Assessment of TAM number, morphology, localization, and distribution within tumor tissues.
Main Results:
- TAMs showed significantly higher immunoreactivity for Iba1 than CD68 (P<0.001).
- Slow-growing GBMs had more CD68+ TAMs in central areas and perivascular regions of the infiltration zone compared to fast-growing GBMs.
- TAM density was higher in central tumor areas than in the infiltration zone for both CD68+ and Iba1+ TAMs.
- TAM morphology varied by location: ramified in the infiltration zone and amoeboid in central areas.
- TAMs were abundant throughout most tumor regions but scarce in necrotic areas.
Conclusions:
- GBMs contain a diverse population of TAMs with morphologies suggesting various activation states.
- Distinct TAM populations are associated with different GBM growth rates, with slow-growing tumors showing specific characteristics.
- Understanding TAM heterogeneity is crucial for elucidating GBM pathogenesis and developing targeted therapies.
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