Faculty, Staff and Student Publications
Publication Date
4-27-2025
Journal
Nature Communications
Abstract
This phase I/II trial aims to evaluate the efficacy of concurrent atezolizumab with radiation therapy and temozolomide (TMZ) followed by adjuvant atezolizumab and TMZ in newly diagnosed glioblastoma (GBM) patients and to identify pre-treatment correlates with outcome (N = 60). Trial number: NCT03174197. The primary outcome was overall survival (OS) whereas secondary outcomes were retrospective global-omics analyses to identify pre-treatment immune and genetic tumor features that correlated with survival. Concurrent use of atezolizumab with radiation and TMZ demonstrated OS in line with published trials for newly diagnosed GBM. Tumor genomic (WES and/or targeted NGS panel), transcriptomic (RNAseq) and tissue microenvironment imaging, as well as fecal metagenomic sequencing were conducted. Gene set enrichment analysis of tumors identified multiple immune-based transcriptomic programs to distinguish patients with longer versus shorter survival (p ≤ 0.01). GBM immune enrichment was highly associated with the pre-treatment tumor mesenchymal subtype and patient gastrointestinal bacterial taxa profile.
Keywords
Humans, Glioblastoma, Gastrointestinal Microbiome, Male, Female, Middle Aged, Brain Neoplasms, Temozolomide, Antibodies, Monoclonal, Humanized, Mutation, Aged, Adult, B7-H1 Antigen, Tumor Microenvironment, Prospective Studies, Immune Checkpoint Inhibitors, Treatment Outcome
DOI
10.1038/s41467-025-56930-7
PMID
40289138
PMCID
PMC12034766
PubMedCentral® Posted Date
4-27-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons