Immunohistochemical Expression of Programmed Death Ligand-1 and CD-8 in Glioblastoma

Abstract

Background Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor in adults. It is characterized by its extremely poor prognosis despite the available treatment strategies. Immune evasion is described in Glioblastoma via the PD-L1/ PD-1 interaction. Programmed death ligand 1 (PD-L1) is a cell surface ligand expressed on the surface of several tumors including GBM and its receptor is the PD-1 (Programmed deasth-1). Other malignant tumors including melanoma and non-small cell lung cancer, showed promising results using PD-L1/PD1 blockade treatment strategies where PD-L1 was described as a potential predictive biomarker for patient selection in these tumors. In our study we will shed the light on the expression and role of PD-L1 in glioblastoma, the presence of tumor infiltrating lymphocytes (TILs) and its interaction with PD-L1 in glioblastoma. The role of PD-L1, CD-8+ TILs, other clinicopathologic parameters and patient’s survival will be also discussed in relation to glioblastoma. Methods Paraffin embedded tissue blocks of thirty cases of GBN were retrieved, slides were prepared and stained via Hx& E for evaluation and confirmation of diagnosis according to the CNS WHO 2016. Immunohistochemistry using PD-L1 and CD-8 was performed on the 30 glioblastoma cases. Interpretation of the results and correlation between the expression of both markers and the clinicopathologic parameters was also done. Furthermore, survival analysis was done to correlate overall survival and progression free survival of the glioblastoma cases to the expression of PD-L1 and CD-8 markers and also the clinicopathologic parameters available. Results Diffuse/fibrillary PD-L1 was expressed in all cases (30/30) with variable percentages (16.7% in ≤ 25% of cases 5/30, 33.3% in > 25%- ≤ 50% of cases10/30, 16.7% in > 50%- ≤ 75% of cases 5/30 and 33.3% in > 75% of cases 10/30). The mean value of Diffuse/fibrillary PD-L1 expression was 57.6%. Membranous PD-L1 was expressed in 6/30 of the cases. TILs were set into two groups according to Han et al 2014; low infiltration group 17/30 (56.7%) of cases and high infiltration group 13/30 (43.3%) of cases. Expression of CD-8 was 10% (median percentage) and 14.3% (mean percentage). PD-L1 and CD-8 correlation was statistically significant (P 0.001) where high PD-L1 expression is associated with low CD-8 expression. PD-L1 expression was associated with worse overall survival (0.001) and worse progression free survival (P 0.026). CD-8expression did not affect the outcome. Correlation of age, sex, tumor site and laterality to outcome were statistically insignificant. In the results of our study PD-L1 expression was the only independent factor that affected the prognosis according to Cox variate analysis. Conclusion The incidence of PD-L1 expression in GBM patients is robust. Higher expression of PD-L1 is associated with lower TILs expression and worse prognosis.