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RNA-seq for identification of therapeutically targetable determinants of immune activation in human glioblastoma.


ABSTRACT: INTRODUCTION:We sought to determine which therapeutically targetable immune checkpoints, costimulatory signals, and other tumor microenvironment (TME) factors are independently associated with immune cytolytic activity (CYT), a gene expression signature of activated effector T cells, in human glioblastoma (GBM). METHODS:GlioVis was accessed for RNA-seq data from The Cancer Genome Atlas (TCGA). For subjects with treatment-naïve, primary GBM, we quantified mRNA expression of 28 therapeutically targetable TME factors. CYT (geometric mean of GZMA and PRF1 expression) was calculated for each tumor. Multiple linear regression was performed to determine the relationship between the dependent variable (CYT) and mRNA expression of each of the 28 factors. Variables associated with CYT in multivariate analysis were subsequently evaluated for this association in an independent cohort of newly diagnosed GBMs from the Chinese Glioma Cooperative Group (CGCG). RESULTS:109 TCGA tumors were analyzed. The final multiple linear regression model included the following variables, each positively associated with CYT except VEGF-A (negative association): CSF-1 (p?=?0.003), CD137 (p?=?0.042), VEGF-A (p?

SUBMITTER: Bagley SJ 

PROVIDER: S-EPMC6342649 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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RNA-seq for identification of therapeutically targetable determinants of immune activation in human glioblastoma.

Bagley Stephen J SJ   Hwang Wei-Ting WT   Brem Steven S   Linette Gerald P GP   O'Rourke Donald M DM   Desai Arati S AS  

Journal of neuro-oncology 20181023 1


<h4>Introduction</h4>We sought to determine which therapeutically targetable immune checkpoints, costimulatory signals, and other tumor microenvironment (TME) factors are independently associated with immune cytolytic activity (CYT), a gene expression signature of activated effector T cells, in human glioblastoma (GBM).<h4>Methods</h4>GlioVis was accessed for RNA-seq data from The Cancer Genome Atlas (TCGA). For subjects with treatment-naïve, primary GBM, we quantified mRNA expression of 28 ther  ...[more]

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