Immunological classification of glioblastoma and its prognostic implications

Am J Transl Res. 2022 Nov 15;14(11):8009-8022. eCollection 2022.

Abstract

Objectives: The progress of immunotherapy for glioblastoma (GBM) is currently slow. To improve immunotherapy, we need a deeper understanding of the immune microenvironment of GBM. Here, we aimed to establish a classification system based on immune expression profile in GBM.

Methods: Immune gene expression profiles of 152 patients with GBM from The Cancer Genome Atlas (TCGA) were used to identify subtypes by consensus clustering, and the classification system was reproduced in the two validation datasets (CGGA and GSE16011). Clinical information, molecular characteristics, immune infiltration, and genomic variation were integrated to characterize the subtypes.

Results: Two distinct immune subtypes in GBM were successfully identified and validated. The Im2 subtype was closely related to IDH-wildtype and combined +7/-10, while the Im1 subtype was associated with IDH mutation. Survival curve analysis showed that the Im2 subtype was associated with significantly shorter survival than the Im1 subtype. Im2 showed a high immune score and stromal score, low tumor purity, enrichment of macrophages, and high immune checkpoint and HLA gene expression. Im1 was characterized by low immune score and stromal score, high tumor purity, enrichment of lymphocytes, and low immune checkpoint and HLA gene expression. Finally, we developed an immune-related signature in GBM with better prognosis prediction.

Conclusions: Our study confirmed the immune heterogeneity of GBM and might provide valuable classification for immunotherapy.

Keywords: Glioblastoma; immune classification; survival; tumor immunity.