Tumor microenvironment in glioblastoma: Current and emerging concepts

Area of Science:

• Neuro-oncology
• Cancer Biology
• Immunology

Background:

• The glioblastoma (GBM) tumor microenvironment (TME) is a complex, heterogeneous system involving cancer cells, resident brain cells, immune cells, and infiltrating marrow-derived cells.
• The TME is dynamic, influenced by cellular composition, cell-cell interactions, metabolic products, pH, and oxygen levels.
• GBM cells actively reprogram the TME, utilizing microenvironmental elements to enhance proliferation, invasion, migration, survival, and treatment resistance.

Purpose of the Study:

• To review current evidence on communication between GBM cells and their TME.
• To discuss models for studying the GBM TME.
• To outline therapeutic strategies targeting TME components.

Main Methods:

• Review of existing scientific literature on glioblastoma and its tumor microenvironment.
• Analysis of cell-cell interactions (direct and indirect signaling).
• Examination of emerging mechanisms like neuron-glioma interfaces.

Main Results:

• GBM cells interact with the TME via direct cell-surface molecule interactions and indirect paracrine/apocrine signaling (cytokines, growth factors, EVs).
• Novel neurotransmitter-based interactions at neuron-glioma interfaces promote tumor survival and growth.
• The TME plays a critical role in GBM progression and therapeutic resistance.

Conclusions:

• Understanding GBM-TME communication is crucial for developing effective cancer therapies.
• Targeting specific components of the TME offers promising therapeutic avenues for glioblastoma.
• Further research into TME dynamics and intercellular communication is warranted.