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, immunosuppression, 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 immunosuppression, which is well documented in glioblastoma.

Experimental Design: To ascertain the association of antigen expression, immunosuppression, 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 antitumor proinflammatory responses, including both adaptive and innate immunity and immunosuppression.

Conclusions: These results indicate that distinct glioma antigens and immune genes show differential expression between glioblastoma subtypes and this may influence responses to immunotherapeutic strategies in patients depending on the subtype of glioblastoma they harbor. Cancer Immunol Res; 1–11. ©2013 AACR.