ACTA FAC MED NAISS 2013;30(4):165-184

Review article

UDC: 616.831-006-097

DOI: 10.2478/afmnai-2013-0009

New Insights Into Molecular Basis of Glioblastoma Multiforme and Associated Immunosuppression

Irena Dimov^1,2, Desanka Tasić^1,3, Ivan Stefanović⁴, Dragan Dimov³

¹University of Niš, Faculty of Medicine, Serbia

²Institute of Immunology Niš, Serbia

³Institute of Pathology Niš, Serbia

⁴Clinic of Neurosurgery, Clinical Center Niš, Serbia


summary

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults and carries the poorest prognosis despite aggressive multimodal therapy. The majority of GBMs develop de novo (primary) with a short clinical history, while secondary GBMs develop through progression from preexisting lower-grade precursor gliomas and show distinct genetic and expression profiles including the high frequency of isocitrate dehydrogenase 1 (IDH1) mutations, already present in precursor lesions. Large-scale integrative genomic studies provided the new view that GBMs are remarkable molecularly heterogeneous tumors and identified distinct molecular entities that may lead to different therapeutic approaches. Although being restricted to the intracranial compartment, GBMs are associated with global immunosuppression. Better understanding of the immune response to GBMs growing in the immunologically distinct microenvironment in the brain and mechanisms by which they may escape the response and even suppress it will accelerate the development of more effective immunotherapies. This review summarizes the current knowledge regarding genetic alterations and signaling pathways critical to the biology of GBMs, few mechanisms of developing local and systemic GBM-induced immunosuppression, and the role of GBM stem cells.

Key words: glioblastoma multiforme, genetics, markers, immunosuppression, glioma stem cells