About this Research Topic
Primary malignant brain tumors (gliomas), as all solid tumors, modify their surrounding microenvironment.
Glioma proliferation has a massive impact on the extracellular milieu, releasing a huge amount of glutamate, ATP, and cytokines. Gliomas are highly invasive. This is due to tumor cells’ ability to synthesize ad hoc enzymes that disrupt the extracellular matrix, allowing tumor cells to grow further, moving across the brain parenchyma.
Because of the tumor’s aggressive invasiveness and dispersal, and in response to neuroinflammation, brain parenchymal cells and immune cells, modulate their activity and functionality. These cells react not only in response to tumor-released molecules, but also to contact with tumor cells.
Primary malignant adult brain cancers are classified as low-grade (astrocytomas and oligodendrogliomas) or high-grade tumors, such as glioblastoma multiforme (GBM) that is the most aggressive subtype of malignant brain tumor, characterized by a 14-month median overall survival. Brain tumor classification relies on histological features such as cellularity, mitotic figures, necrosis, vascularity, and specific gene expression and DNA methylation profiles. Depending on the cancer, surrounding cells react, modifying membrane receptors’ expression, their secretome composition, and their morphology.
Immunohistochemical studies revealed that in the peritumoral brain area, neovascularization and hypoxia markers are expressed, as well GBM invasiveness enhancers, such as transforming growth factor α (TGF-α), stromal cell-derived factor 1 (SDF1/CXCL12), sphingosine-1-phosphate (S1P) and glial cell line-derived neurotrophic factor (GDNF).
Studies focusing on brain parenchyma invasion mechanisms have made gigantic efforts, trying to understand how invasiveness, infiltration, and disease progression can be blocked.
Current treatments include chemotherapy, radiotherapy, and surgical resection. So far, chemotherapy is the only pharmacological approach, able to kill tumor cells.
Parenchymal and immune brain cells have recently drawn attention and have been further examined to shed light on their reactivity within the neuro-inflamed context, exacerbated by the presence of the tumor mass.
In GBM, the blood-brain barrier (BBB) is highly permeable. This is due to an increased expression of adhesion molecules and reduced expression of tight junctions in endothelial cells. A highly permeable BBB allows for infiltrating immune cells’ leakage, above all monocytes, and to a less extent, lymphocytes, particularly T cells.
GBM infiltrating monocytes differentiate into macrophages. These are polarized by tumor cells, together with resident microglia, to an anti-inflammatory pro-tumoral phenotype that can inhibit adaptive immunity by immune checkpoint ligands expression.
Tumor-associated microglia/macrophages (TAMs) engage interactions with tumor cells, supporting neoplastic growth and progression. Although there is still no therapy targeting this cellular interaction, TAMs have recently acquired large visibility as they represent up to 50% of the cells within the GBM mass.
TAMs release tumor-supporting factors, such as transforming growth factor β (TGF-β), stress-inducible protein 1 (STI-1), interleukin-6 (IL-6), IL10, IL-1β, epidermal growth factor (EGF), and C-C motif chemokine ligand 5 (CCL5), enhancing glioma cell growth, migration and invasion.
TAMs are attracted within the tumor mass by a gradient of chemokines (e.g. Cxcl12, Ccl2, and Cx3cl1. Once in the glioma site, microglia is unable to remove apoptotic cells, prune synapses, and protect neuronal precursor cells.
It is still unclear how this change occurs. In addition, little is known regarding TAMs interaction with non-neoplastic cell types within this reprogramming mechanism.
The Research Topic aims to broaden our current knowledge on neurons, astrocytes, microglia, oligodendrocytes, BBB, and immune cells' reaction, to the tumor-induced neuroinflammation state, with an eye of regards to the cellular pathways involved and mechanisms of communication and reaction.
We aim to collect novel studies focusing on parenchymal and immune cells’ reactivity to neuroinflammation, due to the proliferation and invasiveness of brain tumors.
We welcome articles focusing on:
• Brain parenchymal cells ‘reaction mechanisms against tumor-induced neuroinflammation
• Tumor-induced neuroinflammation enhancement/tackling by microglia and infiltrating immune cells
• BBB permeability modification in the brain tumor context
Glioma proliferation has a massive impact on the extracellular milieu, releasing a huge amount of glutamate, ATP, and cytokines. Gliomas are highly invasive. This is due to tumor cells’ ability to synthesize ad hoc enzymes that disrupt the extracellular matrix, allowing tumor cells to grow further, moving across the brain parenchyma.
Because of the tumor’s aggressive invasiveness and dispersal, and in response to neuroinflammation, brain parenchymal cells and immune cells, modulate their activity and functionality. These cells react not only in response to tumor-released molecules, but also to contact with tumor cells.
Primary malignant adult brain cancers are classified as low-grade (astrocytomas and oligodendrogliomas) or high-grade tumors, such as glioblastoma multiforme (GBM) that is the most aggressive subtype of malignant brain tumor, characterized by a 14-month median overall survival. Brain tumor classification relies on histological features such as cellularity, mitotic figures, necrosis, vascularity, and specific gene expression and DNA methylation profiles. Depending on the cancer, surrounding cells react, modifying membrane receptors’ expression, their secretome composition, and their morphology.
Immunohistochemical studies revealed that in the peritumoral brain area, neovascularization and hypoxia markers are expressed, as well GBM invasiveness enhancers, such as transforming growth factor α (TGF-α), stromal cell-derived factor 1 (SDF1/CXCL12), sphingosine-1-phosphate (S1P) and glial cell line-derived neurotrophic factor (GDNF).
Studies focusing on brain parenchyma invasion mechanisms have made gigantic efforts, trying to understand how invasiveness, infiltration, and disease progression can be blocked.
Current treatments include chemotherapy, radiotherapy, and surgical resection. So far, chemotherapy is the only pharmacological approach, able to kill tumor cells.
Parenchymal and immune brain cells have recently drawn attention and have been further examined to shed light on their reactivity within the neuro-inflamed context, exacerbated by the presence of the tumor mass.
In GBM, the blood-brain barrier (BBB) is highly permeable. This is due to an increased expression of adhesion molecules and reduced expression of tight junctions in endothelial cells. A highly permeable BBB allows for infiltrating immune cells’ leakage, above all monocytes, and to a less extent, lymphocytes, particularly T cells.
GBM infiltrating monocytes differentiate into macrophages. These are polarized by tumor cells, together with resident microglia, to an anti-inflammatory pro-tumoral phenotype that can inhibit adaptive immunity by immune checkpoint ligands expression.
Tumor-associated microglia/macrophages (TAMs) engage interactions with tumor cells, supporting neoplastic growth and progression. Although there is still no therapy targeting this cellular interaction, TAMs have recently acquired large visibility as they represent up to 50% of the cells within the GBM mass.
TAMs release tumor-supporting factors, such as transforming growth factor β (TGF-β), stress-inducible protein 1 (STI-1), interleukin-6 (IL-6), IL10, IL-1β, epidermal growth factor (EGF), and C-C motif chemokine ligand 5 (CCL5), enhancing glioma cell growth, migration and invasion.
TAMs are attracted within the tumor mass by a gradient of chemokines (e.g. Cxcl12, Ccl2, and Cx3cl1. Once in the glioma site, microglia is unable to remove apoptotic cells, prune synapses, and protect neuronal precursor cells.
It is still unclear how this change occurs. In addition, little is known regarding TAMs interaction with non-neoplastic cell types within this reprogramming mechanism.
The Research Topic aims to broaden our current knowledge on neurons, astrocytes, microglia, oligodendrocytes, BBB, and immune cells' reaction, to the tumor-induced neuroinflammation state, with an eye of regards to the cellular pathways involved and mechanisms of communication and reaction.
We aim to collect novel studies focusing on parenchymal and immune cells’ reactivity to neuroinflammation, due to the proliferation and invasiveness of brain tumors.
We welcome articles focusing on:
• Brain parenchymal cells ‘reaction mechanisms against tumor-induced neuroinflammation
• Tumor-induced neuroinflammation enhancement/tackling by microglia and infiltrating immune cells
• BBB permeability modification in the brain tumor context
Keywords: Gliomas, GBM, Phenotypic plasticity, tumor microenvironment, Neuroinflammation, Tumor-associated macrophages, Infiltration
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