Improved overall survival in an anti-PD-L1 treated cohort of newly diagnosed glioblastoma patients is associated with distinct immune, mutation, and gut microbiome features: a single arm prospective phase I/II trial
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.
Authors
- Marta Peñas-Prado
- Scott E. Woodman (ORCID: https://orcid.org/0000-0002-1157-6991)
- W.K. Alfred Yung (ORCID: https://orcid.org/0000-0002-1669-0793)
- Nadim J. Ajami (ORCID: https://orcid.org/0000-0002-3808-8576)
- Katja Schulze (ORCID: https://orcid.org/0000-0003-3704-5651)
- Jennifer Ann Wargo (ORCID: https://orcid.org/0000-0003-3438-7576)
- Brian McKinley (ORCID: https://orcid.org/0000-0001-7105-9649)
- Edwin R. Parra (ORCID: https://orcid.org/0000-0001-9068-1636)
- Rebecca A. Harrison (ORCID: https://orcid.org/0000-0002-5689-8492)
- Sharia Hernandez (ORCID: https://orcid.org/0000-0002-7746-0860)
- Shiao‐Pei Weathers (ORCID: https://orcid.org/0000-0002-0405-102X)
- John de Groot (ORCID: https://orcid.org/0000-0003-1454-6461)
- Walter C. Darbonne (ORCID: https://orcid.org/0000-0002-4386-1826)
- Xiqi Li
- Monica Loghin
- Dipen M. Maru (ORCID: https://orcid.org/0000-0002-9134-7709)
- Haifeng Zhu (ORCID: https://orcid.org/0000-0001-7315-4105)
- P. Andrew Futreal (ORCID: https://orcid.org/0000-0001-8663-2671)
- Ashish Damania (ORCID: https://orcid.org/0009-0001-3158-2846)
- Nazanin Majd (ORCID: https://orcid.org/0000-0001-6451-544X)
- Heather Yan Lin (ORCID: https://orcid.org/0000-0002-1779-7007)
- Carlos Kamiya Matsuoka (ORCID: https://orcid.org/0000-0003-3216-2728)
- Luisa M. Solis Soto (ORCID: https://orcid.org/0000-0002-1253-630X)
- Mark Knafl (ORCID: https://orcid.org/0000-0002-3953-2173)
- Ignacio Wistuba
- Barbara O’Brien
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Kaiser Permanente San Francisco Medical Center (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-27
- DOI
- https://doi.org/10.1038/s41467-025-56930-7
- Citations
- 15
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 15.68
Funders
- Genentech
- University of Texas MD Anderson Cancer Center