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PD-L1 expression in medulloblastoma: an evaluation by subgroup. Oncotarget Martin, A. M., Nirschl, C. J., Polanczyk, M. J., Bell, W. R., Nirschl, T. R., Harris-Bookman, S., Phallen, J., Hicks, J., Martinez, D., Ogurtsova, A., Xu, H., Sullivan, L. M., Meeker, A. K., Raabe, E. H., Cohen, K. J., Eberhart, C. G., Burger, P. C., Santi, M., Taube, J. M., Pardoll, D. M., Drake, C. G., Lim, M. 2018; 9 (27): 19177–91

Abstract

Background: This study evaluated the expression of PD-L1 and markers of immune mediated resistance in human medulloblastoma (MB), the most common malignant pediatric brain tumor.Results: Overall levels of PD-L1 in human MB were low; however, some cases demonstrated robust focal expression associated with increased immune infiltrates. The case with highest PD-L1 expression was a sonic hedgehog (SHH) MB. In cell lines, SHH MB, which are low-MYC expressing, demonstrated both constitutive and inducible expression of PD-L1 while those in Group 3/4 that expressed high levels of MYC had only inducible expression. In vitro, IFN-gamma robustly stimulated the expression of PD-L1 in all cell lines while radiation induced variable expression. Forced high MYC expression did not significantly alter PD-L1.Methods: Human MB tumor samples were evaluated for expression of PD-L1 and immune cell markers in relation to molecular subgroup assignment. PD-L1 expression was functionally analyzed under conditions of interferon gamma (IFN-gamma), radiation, and MYC overexpression.Conclusions: MB expresses low levels of PD-L1 facilitating immune escape. Importantly, TH1 cytokine stimulation appears to be the most potent inducer of PD-L1 expression in vitro suggesting that an inflamed tumor microenvironment is necessary for PD-1 pathway activation in this tumor.

View details for DOI 10.18632/oncotarget.24951

View details for PubMedID 29721192