Abstract

Variations in the tumor immune microenvironment between Glioblastoma (GBM) patients complicates development and testing of immunotherapies. We used publicly available single cell RNA sequencing data of GBM patients to extract pan immune-specific genes in GBM. Interrogating bulk GBM sequencing or microarray data with pan immune-specific genes should allow examination of the immune component. We used pan immune-specific genes to investigate subtypes of GBM immune microenvironments. Consensus clustering using these genes on GBM TCGA RNAseq data gave 4 distinct subtypes while 12% of tumors were not assigned to any of those subtypes. Immune subtypes had distinct clinical outcomes. Differences in median survival (16.6 vs 5.8 months; longest vs. shortest survival; p < 1e-05 Logrank, Wald and Likelihood ratio tests) suggests the immune microenvironment significantly impacts clinical course. Cox univariate analysis indicates age had no contribution to risk (HR = 1.034; 95% confidence interval 1.017-1.052). We propose that immune-subtyping of GBM with pan immune-specific genes will lead to biomarkers that predict immunotherapeutic response. It will also help to identify molecular pathways and targets that suppress the immune anti-tumor response.

Speaker Bio

Dr. Anna Joy is a Research Associate Professor in the Center for Computational Systems Biology. Her research focus is to understand mechanisms of tumorigenesis, progression and therapy resistance in Glioblastoma brain tumors for discovery of novel drug targets and treatment biomarkers. She has elucidated an unexpected role for a member of the PI3K/AKT tumor driver pathway that has consequences for pathway inhibitors. She is currently developing a biomarker that shows promise in identifying the immune microenvironment of Glioblastoma patients and may be used for immunotherapy selection.