Immune heterogeneity of glioblastoma subtypes: extrapolation from the cancer genome atlas

Abstract

Purpose: The molecular heterogeneity of glioblastoma has been well recognized and has resulted in the generation of molecularly defined subtypes. These subtypes (classical, neural, mesenchymal, and proneural) are associated with particular signaling pathways and differential patient survival. Less understood is the correlation between these glioblastoma subtypes with immune system effector responses, immune suppression and tumor-associated and tumor-specific antigens. The role of the immune system is becoming increasingly relevant to treatment as new agents are being developed to target mediators of tumor-induced immune suppression which is well documented in glioblastoma.

Experimental design: To ascertain the association of antigen expression, immune suppression, and effector response genes within glioblastoma subtypes, we analyzed the Cancer Genome Atlas (TCGA) glioblastoma database.

Results: We found an enrichment of genes within the mesenchymal subtype that are reflective of anti-tumor proinflammatory responses, including both adaptive and innate immunity and immune suppression.

Conclusions: These results indicate that distinct glioma antigens and immune genes demonstrate differential expression between glioblastoma subtypes and this may influence responses to immune therapeutic strategies in patients depending on the subtype of glioblastoma they harbor.

Keywords: glioblastoma; immune activation; immune suppression; tumor antigens.

Fig. 1

Venn diagrams demonstrating immune activators (left) and immune suppressors (right) that are differentially expressed at a FDR of 0.001.

Fig. 2

Heatmaps of the 734 immune activator genes (left column) and 218 immune suppressor genes (right column) compared between glioblastoma subtypes. The expression values shown on the heatmap have been standardized and at ±2 standard deviations for display purposes. The scale of the values is indicated in the color key.