Dimov I.,University of Niš |
Dimov I.,Institute of Immunology Nis |
Tasic D.,University of Niš |
Tasic D.,Institute of Pathology Nis |
And 2 more authors.
Acta Facultatis Medicae Naissensis | Year: 2013
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 lowergrade 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.