Abstract
BACKGROUND
Glioblastoma is a high-grade glioma and is considered the most aggressive primary brain tumor with a median overall survival of 11–15 months. Methylation of the promoter of the MGMT gene, which encodes a DNA repair protein, has been shown to be a good prognostic indicator for GBM survival. It is known that GBM has elevated expression of several immune checkpoint molecules that allow the tumor to evade anti-tumor immune response. Therefore, it is important to elucidate connections between prognostic factors like methylation status and immunologic markers in the tumor microenvironment (TME) that might lead to immunosuppression.
METHODS
Patients with resected GBM tumor samples were identified by pathology reports as having tumors with either methylated or unmethylated MGMT promoters. Corresponding patient tumor biopsy samples were embedded in paraffin, sectioned, and then stained using specific antibodies for known immune checkpoint molecules: PD-1, PD-L1, LAG-3, TIM-3, CSF1R, and IDO-1.
RESULTS
In our cohort of 34 patients, 17 had methylated MGMT promoter regions and 17 did not. We found no statistically significant difference between methylated and unmethylated MGMT promoter status for immune checkpoint expression. However, we did find a statistically significant negative correlation (P< 0.05) between the degree of PD-L1 expression in the TME and the progression free survival of patients with the MGMT promoter methylation phenotype.
CONCLUSION
Our study examined the relationship between immune checkpoint markers and methylation status of MGMT promoters in GBM. While there was no statistically significant difference between these two groups within the immunological framework of this study, there was a statistically significant negative correlation showing that increased PD-L1 expression in patients with methylated MGMT promoter tumors correlated to a worse progression free survival. Future studies are indicated to investigate the correlation between PD-L1 expression in relation to GBM treatment prognosis and its dependence on MGMT promoter methylation.