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In this issue of Neuro-Oncology, Berghoff et al present the results of their investigations into the expression of programmed death-ligand 1 (PD-L1) in human glioblastoma specimens and their relationship to other tissue-based and clinical parameters. In specimens from adults with newly diagnosed or recurrent glioblastoma, the investigators reported that diffuse/fibrillary PD-L1 expression of variable extent was found in more than 70% of glioblastoma specimens, with a higher proportion in newly diagnosed cases. Furthermore, more than 70% of cases showed evidence of high tumor-infiltrating lymphocyte (TIL) infiltration, although most were of sparse-to-moderate density. In glioblastoma samples from the Cancer Genome Atlas, the relationships between PD-L1 expression, molecular subtypes, and clinical outcomes were explored. Samples with known molecular subtypes were then classified according to their level of PD-L1 expression (high or low), and a significant difference in the distribution of PD-L1 high and low groups was found across molecular subtypes, with the mesenchymal subtype in particular having a high level of PD-L1 expression and the proneural and G-CIMP subtypes primarily having low expression of PD-L1. The anti-PD-L1 antibody, 5H1, used in this study is not commercially available, although its use has been confirmed in other experiments, whereas some commercially available antibodies have failed to show reliable PD-L1 labeling.1 The authors conclude that PD-L1 expression and TILs were found in most of the glioblastoma samples they evaluated, but a relationship between these parameters and outcome was not observed. Still, the high expression of PD-L1 in these glioblastoma samples suggests that it may be a valid target for further clinical investigation.

Programmed death ligand 1 (PD-L1) as an immunotherapy target in patients with glioblastoma: Table 1.