Four distinct immunologic groups were identified and correlated with overall survival (OS) in patients with high-grade glioma. The study findings were recently reported in Cancer Immunology Research.
Gene-expression profiles were obtained from 9 studies, and the combined data set included 1135 adult and pediatric patients with high-grade gliomas. Because the transcriptional subtype was unknown for 640 samples, and mutational status unknown for 472, machine learning was used to predict this missing information.
The composition of immune and stromal cell gene expression was analyzed, revealing 4 clusters: vascular dominant (immune 1), monocytic and stromal dominant (immune 2), monocytic and T-cell dominant (immune 3), and antigen-presenting cell, natural killer cell, and T-cell dominant (immune 4).
These clusters were associated with transcriptional subtypes. Immune 1 was associated with the classic transcriptional subtype. Immunes 2 and 3 were associated with a mesenchymal signature. Immune 4, however, was not associated with any particular transcriptional subtype. Furthermore, patient age was not found to be associated with any of the 4 clusters.
When OS data were analyzed, associations between immune cell signatures and OS were revealed. Cases with a monocytic and stromal signature (immune 2) had significantly worse OS. The best OS was seen in cases with immune clusters dominated by antigen-presenting cells, natural killer cells, and T cells (immune 4).
“Taken together, our study demonstrates that future immunotherapeutic strategies should take into account the distinct immunologic landscapes that may modulate therapeutic efficacy, especially for rare mutational subgroups of high-grade gliomas,” the study authors wrote.
Bockmayr M, Klauschen F, Maire CL, et al. Immunologic profiling of mutational and transcriptional subgroups in pediatric and adult high-grade gliomas. Cancer Immunol Res. 2019;7(9):1401-1411.