Shiao-Pei Weathers, Xiqi Li, Haifeng Zhu, Ashish V. Damania, Mark Knafl, Brian McKinley, Heather Lin, Rebecca A. Harrison, Nazanin K. Majd, Barbara J. O’Brien, Marta Penas-Prado, Monica Loghin, Carlos Kamiya-Matsuoka, W. K. Alfred Yung, Luisa M. Solis Soto, Dipen M. Maru, Ignacio Wistuba, Edwin R. Parra Cuentas, Sharia Hernandez, Andrew Futreal, Jennifer A. Wargo, Katja Schulze, Walter C. Darbonne, Nadim J. Ajami, Scott E. Woodman, John F. de Groot
{"title":"一项单臂前瞻性I/II期临床研究表明,接受抗pd - l1治疗的新诊断胶质母细胞瘤患者总体生存率的提高与独特的免疫、突变和肠道微生物组特征相关","authors":"Shiao-Pei Weathers, Xiqi Li, Haifeng Zhu, Ashish V. Damania, Mark Knafl, Brian McKinley, Heather Lin, Rebecca A. Harrison, Nazanin K. Majd, Barbara J. O’Brien, Marta Penas-Prado, Monica Loghin, Carlos Kamiya-Matsuoka, W. K. Alfred Yung, Luisa M. Solis Soto, Dipen M. Maru, Ignacio Wistuba, Edwin R. Parra Cuentas, Sharia Hernandez, Andrew Futreal, Jennifer A. Wargo, Katja Schulze, Walter C. Darbonne, Nadim J. Ajami, Scott E. Woodman, John F. de Groot","doi":"10.1038/s41467-025-56930-7","DOIUrl":null,"url":null,"abstract":"<p>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 (<i>N</i> = 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 (<i>p</i> ≤ 0.01). GBM immune enrichment was highly associated with the pre-treatment tumor mesenchymal subtype and patient gastrointestinal bacterial taxa profile.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"3 1","pages":""},"PeriodicalIF":15.7000,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"Shiao-Pei Weathers, Xiqi Li, Haifeng Zhu, Ashish V. Damania, Mark Knafl, Brian McKinley, Heather Lin, Rebecca A. Harrison, Nazanin K. Majd, Barbara J. O’Brien, Marta Penas-Prado, Monica Loghin, Carlos Kamiya-Matsuoka, W. K. Alfred Yung, Luisa M. Solis Soto, Dipen M. Maru, Ignacio Wistuba, Edwin R. Parra Cuentas, Sharia Hernandez, Andrew Futreal, Jennifer A. Wargo, Katja Schulze, Walter C. Darbonne, Nadim J. Ajami, Scott E. Woodman, John F. de Groot\",\"doi\":\"10.1038/s41467-025-56930-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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 (<i>N</i> = 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 (<i>p</i> ≤ 0.01). GBM immune enrichment was highly associated with the pre-treatment tumor mesenchymal subtype and patient gastrointestinal bacterial taxa profile.</p>\",\"PeriodicalId\":19066,\"journal\":{\"name\":\"Nature Communications\",\"volume\":\"3 1\",\"pages\":\"\"},\"PeriodicalIF\":15.7000,\"publicationDate\":\"2025-04-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Communications\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41467-025-56930-7\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-56930-7","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
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.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.