Mohammad Amin Dehghani - Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Seyyed Hossein Hassanpour Ezzati - Young Researchers and Elite Club, Yasooj Branch, Islamic Azad University, Yasooj, Iran
Fatemeh Dehghani - Department of Genetics, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Golnoosh Alikarami - School of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran

Introduction: Glioblastoma multiforme (GBM) is recognized as an aggressive primary brain tumor. In general, GBM activates different immune escape mechanisms and has been identified as an immunosuppressive neoplasm. Lately, durable tumor remissions in numerous types of cancer and high response rates in terms of clinically-relevant enhancements have been associated with the application of immune checkpoint inhibitors) anti-PD-1 and anti- CTLA-4).Methods: In this study, we searched the PubMed database to find English articles related to our topic applying the keywords of GBM, immune checkpoint inhibitors, CTLA-4 inhibitor, PD-1 inhibitor and therapeutic strategies.Results: Checkpoint regulators have been recognized as a favorable GBM treatment since the use of checkpoint inhibitors in cancer immunotherapy. Researchers performed the first extensive phase three trials in 2014 to evaluate the safety and efficiency of nivolumab in GBM patients, followed by another large phase III trial of nivolumab in patients diagnosed with GBM. The integration of radiation and checkpoint inhibitors has been assessed in various clinical studies. Moreover, researchers are currently examining the concomitant use of checkpoint inhibitors and common treatments, such as corticosteroids, radiotherapy, temozolomide, and bevacizumab by conducting relevant clinical trials. Mortality rate of patients with brain metastases can reduced in case of simultaneous application of radiotherapy and ipilimumab. The importance of assessing the role of immune checkpoint inhibitors in GBM is justified by considering the success rate of immunotherapy in other cancers and our recent comprehension of the link between the immune system and the brain. Conclusion: It is recommended that GEMM of GBMs be used by researchers in future studies to improve the effectiveness of immunotherapy on GBM and assess the mechanisms of immune responses made against tumors so that optimized, novel, and appropriate checkpoint blockade treatments could be designed for this deadly cancer.

GBM, immune checkpoint inhibitors, CTLA-4 inhibitor, PD-1 inhibitor, therapeutic strategies