CNS macrophages and peripheral myeloid cells in brain tumours

Abstract

However, it is also becoming evident that some myeloid-directed glioma therapies may only be beneficial for distinct subclasses of gliomas and that a more cell-type specific manipulation of either microglia or macrophages may improve therapeutic outcome. 2 Neuropathological features of gliomasGlial tumours constitute approximately 50% of all newly diagnosed primary brain tumours, with low-grade gliomas accounting for roughly 15% of all brain tumours in adults [106]. The morphology and the cellular markers for gliomas share some similarities with the main macroglial cell-types (i.e. astrocytes, oligodendrocytes) [75].Histopathologically, gliomas are divided into four different grades (according to the classification scheme by the world health organization, WHO), in which low-grade tumours are defined as grade-I/-II and high-grade gliomas as grade-III and-IV [87]. The presence of mitotic activity is a key feature for distinguishing low-grade from high-grade gliomas [75]. Statistically, low-grade astrocytomas arise roughly in proportion to the relative mass of the different lobes with most common location within the frontal lobes, followed by temporal and parietal lobe lesions [107]. Overall, 5-and 10-year survival rates of ~70% and 50% for grade-I and grade-II gliomas, respectively, have been reported in the literature [25]. The tumour tissue has no obvious signs of neoangiogenesis, infiltrative invasion or inflammation [75]. On the contrary, the outlook for patients with high-grade gliomas is grim. The majority of individuals diagnosed with a grade-IV glioma, which are very heterogeneous tumours and therefore also named glioblastoma multiforme (GBM), have a median progression-free survival of just over half a year and median overall survival of 15-18 months [17], only some subpopulations of patients show median survivals of almost 2 years [54]. GBM is a fast growing, highly angiogenic and invasive tumour and the diffuse growth is a major obstacle for GBM therapy. Other hallmarks of malignant gliomas are break-down of the blood-brain barrier (BBB), many hypoxic areas and necrotic centres [75]. Gliomas are usually diagnosed by neurorimaging (i.e. magnetic resonance imaging) and visualisation of the uptake of a contrast-enhancing agent within the tissue indicates BBB-leakage/breakdown [159]. GBM typically presents as a ragged contrast-enhanced and complex multi-cystic structure. GBM may be diagnosed de novo, i.e. in patients without a clinical history for brain tumours (then named primary GBM) or may evolve from lower grade gliomas (secondary GBM) [103].3 Multi-modal glioma therapyGlioma therapy comprises very different strategies. For patients with deep-seated lesions or lesions located in eloquent regions which are clinically and radiographically indicated as low-grade glioma a conservative management including regular neuroimaging (after obtaining a histological diagnosis) [165], see also [130,150]. Individuals with high-grade gliomas undergo multi-modal treatment combining cytoreductive surgery, radiation-and ch...

Glioblastoma cells induce differential glutamatergic gene expressions in human tumor-associated microglia/macrophages and monocyte-derived macrophages

“…Analyses of surgically resected glioblastoma tissues show that as much as 30% of the tissue consisted of tumorassociated microglia/macrophages (TAMs), 5,6 which are derived from parenchymal microglia in the brain and monocytes-derived macrophages from the blood. 7,8 These analyses moreover show that the number of TAMs in the tumor region correlated with the histological grade of gliomas. 9,10 TAMs in the presence of glioma cells become immunosuppressive and elicit an anti-inflammatory response by increasing the expression and release of cytokines such as IL-10 and VEGF, thereby contributing to a milieu that promotes the survival and growth of the glioblastoma cells.…”

Molecular profiling of long-term survivors identifies a subgroup of glioblastoma characterized by chromosome 19/20 co-gain

“…While the so-called M1 cells exhibit anti-tumor activity, the M2 phenotype supports tumor cell growth and invasion, a finding which also applies to brain tumors (reviewed in [18]). …”

Distribution and characterization of tumor-associated macrophages/microglia in rat C6 glioma

“…In recent years, accumulated data have established that the immune network may be involved in regulating glioma development and growth (2). Moreover, tumor cells have been killed following direct immunization experiments using vaccines in mice, indicating its role in specific protective immunity and tumor destruction mediated by immune cells, such as microglia/macrophages (3). These immunotherapies exert a highly specific, long-term fatal effect on tumor cells by stimulating and supplementing the body's antitumor immunity (4,5), with only minimal adverse reactions (6).…”