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Translocator protein (TSPO) expression in neoplastic cells and tumor-associated macrophages in meningiomas
Nadja Blum1, Christian Mirian1, Andrea Daniela Maier1,2
1Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark.
Abstract:
Meningiomas are the most common primary intracranial tumors and show extensive infiltration of macrophages. The mitochondrial membrane protein translocator protein (TSPO) has been used as an in vivo marker of microglia and macrophage activation to visualize neuroinflammation. However, it is unknown which cell types express TSPO in meningiomas. Immunohistochemistry of 38 WHO grade 1-3 meningiomas was subjected to segmentation and deep learning classification of TSPO expression to either Iba1-positive tumor-associated macrophages (TAMs) or all other (mainly neoplastic) cells. A possible association between clinical data and TSPO expression intensities was also investigated. TAMs accounted for 15.9%-26% of all cells in the meningioma tissue. Mean fluorescence intensity of TSPO was significantly higher in TAMs (p < 0.0001), but the mass of neoplastic cells in the tumors exceeded that of TAMs. Thus, the summed fluorescence intensity of TSPO in meningioma cells was 64.1% higher than in TAMs (p = 0.0003). We observed no correlation between TSPO expression intensity and WHO grade. These results indicate that both macrophage-lineage and neoplastic cells in meningiomas express TSPO and that the SPECT-TSPO signal in meningiomas mainly reflects the latter; TSPO is expressed equally in parenchymal activated and resting macrophage/microglia lineage cells.
Insights
Translocator protein (TSPO) is expressed in both neoplastic cells and tumor-associated macrophages in meningiomas. Despite higher intensity in macrophages, neoplastic cells contribute more to the overall TSPO signal, impacting neuroinflammation imaging.
Area of Science:
- Neuro-oncology
- Immunology
- Molecular Imaging
Background:
- Meningiomas are common primary brain tumors with significant macrophage infiltration.
- Translocator protein (TSPO) is a marker for activated microglia and macrophages, used to visualize neuroinflammation.
- The cellular source of TSPO expression in meningiomas remains unclear.
Purpose of the Study:
- To investigate TSPO expression in different cell types within meningiomas.
- To determine whether TSPO expression correlates with tumor grade or clinical data.
- To clarify the contribution of neoplastic cells versus macrophages to the overall TSPO signal in meningiomas.
Main Methods:
- Immunohistochemistry was performed on 38 WHO grade 1-3 meningiomas.
- Deep learning and segmentation classified TSPO expression in Iba1-positive tumor-associated macrophages (TAMs) and other neoplastic cells.
- Analysis included quantification of TSPO intensity and correlation with clinical data.
Main Results:
- Tumor-associated macrophages constituted 15.9%-26% of cells in meningioma tissue.
- Mean TSPO fluorescence intensity was significantly higher in TAMs compared to other cells (p < 0.0001).
- However, summed TSPO fluorescence intensity was 64.1% higher in neoplastic cells due to their greater mass (p = 0.0003).
- No correlation was found between TSPO expression intensity and WHO grade.
Conclusions:
- Both neoplastic cells and macrophage-lineage cells express TSPO in meningiomas.
- The primary source of the in vivo TSPO signal in meningiomas is likely the neoplastic cells.
- TSPO expression is consistent across activated and resting macrophage/microglia lineage cells in the tumor microenvironment.
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