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The microglial/macrophagic response at the tumour-brain border of invasive meningiomas
S Grund1, J Schittenhelm, F Roser
1Institute of Brain Research, Univeristy of Tübingen, Tübingen, Germany.
Aims:
Little is known about the immune response of the brain to invasive meningiomas. The present study was based upon the hypothesis that the microglial/macrophagic response towards brain-invasive meningiomas is dependent on the intactness of the pial-glial basement membrane.
Methods:
We immunostained sections from 40 brain-invasive meningiomas that were graded according to World Health Organization (WHO) 2007 criteria. Thirty-three tumours were histologically WHO grade II (18, 'otherwise benign', and 15, 'otherwise atypical'), and seven, grade III. Microglial/macrophagic cells were labelled with antibodies directed against major histocompatibility complex class II, CD68, CD14 and CD163. Anti-collagen IV was used to visualize basement membranes.
Results:
Twenty-five per cent (10/40) meningiomas (1/18 WHO grade II 'otherwise benign', 3/15 grade II 'otherwise atypical' and 6/7 WHO grade III) contained microglial/macrophagic cells at the tumour-brain border. The presence of these cells correlated with the absence of the pial-glial basement membrane (BM) and with WHO grade III. The monocytic response was of two kinds: one consisted of a dense layer of mononuclear cells at the tumour-brain border in nine cases, the other of an elevated number of microglial cells expressing CD14 or CD163 (two cases).
Conclusions:
The immune response at the tumour-brain interface correlates with the absence of the pial-glial BM and with malignancy grade. It remains to be established whether the mononuclear cells at the tumour-brain border are native microglia or blood-derived macrophages.
Insights
The brain
Area of Science:
- Neuro-oncology
- Neuroimmunology
- Brain Tumor Immunology
Background:
- The immune response within the brain to invasive meningiomas is not well understood.
- The pial-glial basement membrane's role in modulating this response is unknown.
Purpose of the Study:
- To investigate the relationship between the microglial/macrophagic response and the integrity of the pial-glial basement membrane in brain-invasive meningiomas.
- To correlate the immune cell infiltration with tumor grade and basement membrane status.
Main Methods:
- Immunohistochemical analysis of 40 brain-invasive meningiomas (WHO grades II and III).
- Assessment of microglial/macrophagic cells using markers (MHC class II, CD68, CD14, CD163).
- Evaluation of pial-glial basement membrane integrity using anti-collagen IV staining.
Main Results:
- Microglial/macrophagic cells were present at the tumor-brain border in 25% of cases.
- The presence of these immune cells correlated significantly with the absence of the pial-glial basement membrane and higher World Health Organization (WHO) grade III.
- Two distinct patterns of monocytic infiltration were observed: a dense border layer and increased microglial expression of CD14/CD163.
Conclusions:
- The immune response at the tumor-brain interface in invasive meningiomas is associated with basement membrane disruption and higher tumor malignancy.
- Further research is needed to determine the origin of these infiltrating mononuclear cells (resident microglia vs. blood-derived macrophages).
