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Immunotherapy in the Treatment of Glioblastoma
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Sadegh Shirian   , Kimia Mansouri Boroujeni * , Mohammad Reza Tashakor , Ebrahim Kahyani |
| Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran , kimiamansouri7878@gmail.com |
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Abstract: (10 Views) |
Introduction: Glioblastoma (GBM), recognized as the most common and aggressive primary malignant tumor of the central nervous system in adults, continues to be associated with recurrence and limited survival despite aggressive interventions. This review study, through a comprehensive analysis of the latest findings in immunotherapy, examines treatment challenges, tumor resistance mechanisms, and the results of clinical trials in this field. Based on the evidence in these studies, Immune Checkpoint Inhibitors have not significantly increased survival in patients with GBM. This may be due to the low immunogenicity and low mutation rate of GBM cells, the immunosuppressive tumor microenvironment, and the use of drugs such as corticosteroids that impair T-lymphocyte function. Furthermore, the blood–brain barrier represents a physical obstacle that limits the effective delivery of therapeutic agents and the access of immune cells to the tumor. Nevertheless, several novel therapeutic approaches have been developed to overcome these challenges. Although chimeric antigen receptor T-cell therapy continues to face significant limitations, clinical trials involving intraventricular administration have demonstrated effective results. Multi-antigen vaccines have shown improved clinical efficacy, particularly when administered during the early stages of disease. In patients with newly diagnosed GBM, the addition of dendritic cell–based vaccination to standard treatment increased median overall survival from 16.5 to 19.3 months. Furthermore, oncolytic viruses have induced durable responses in certain patient subgroups. However, the pronounced antigenic heterogeneity of GBM cells, together with their diverse mechanisms of immune evasion, suggests that monotherapy with a single immunotherapeutic approach is unlikely to produce sustained and clinically meaningful responses. These challenges highlight the potential need for multimodal immunotherapeutic strategies capable of targeting multiple tumor antigens and overcoming distinct mechanisms of immune resistance. Conclusion: The future of GBM treatment should be built upon the development of combined and multimodal therapies aiming at simultaneously targeting tumor signaling pathways and modifying its microenvironment to overcome therapeutic resistance and increase patient survival.
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| Keywords: Brain, Central Nervous System, Tumor Microenvironment, Combined Modality Therapy |
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Full-Text [PDF 875 kb]
(3 Downloads)
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Type of Study: Review --- Open Access, CC-BY-NC |
Subject:
Neuroimmunology
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