Gliomas are the most common type of primary brain tumor and include glioblastoma (GBM), which is the most lethal form of the disease, and remains a significant, unmet clinical need (1). Contrary to conventional notions of central nervous system immuneprivilege, there is indeed extensive cross-talk between the immune system and tumors in the brain. Several successful immune therapies are either in development or have received recent approval from the Food and Drug Administration across a broad array of cancers (Table 1). However, the results for immune therapy against solid tumors in the brain have been less dramatic to date.

A recent manuscript by Berghoff and colleagues offers one reason why certain patients with glioma may not respond as well to immune-based treatment. By segregating gliomas into distinct molecular classes based primarily on the mutational status of isocitrate dehydrogenase 1 and 2 genes (IDH1/2), it was demonstrated that gliomas characterized by wild-type IDH (IDH-wt) displayed a greater number of tumor-infiltrating lymphocytes (TILs) and elevated expression of the immunosuppressive molecule programmed death ligand 1 (PD-L1) when compared to their IDH mutant (IDH-mut) counterparts. This association was recapitulated at the gene expression level by data derived from The Cancer Genome Atlas (TCGA). Although not demonstrated explicitly, one extrapolation the authors suggest is that IDH-wt gliomas may in fact be more “immunologically active” than IDH-mut gliomas and thus more easily targeted by PD-1/PD-L1 checkpoint blockade. That is to say, elevated levels of PD-L1 expression found in IDH-wt glioma, while perhaps associated with baseline immune suppression, may provide a prime opportunity for therapeutic intervention in these tumors.