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

IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
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
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引用次数: 0

摘要

这项I/II期试验旨在评估atezolizumab与放疗和替莫唑胺(TMZ)并发治疗对新诊断的胶质母细胞瘤(GBM)患者的疗效,并确定治疗前与预后的相关性(N = 60)。试验号:NCT03174197。主要结局是总生存期(OS),次要结局是回顾性全球组学分析,以确定治疗前与生存相关的免疫和遗传肿瘤特征。atezolizumab与放疗和TMZ同时使用表明,新诊断的GBM的OS与已发表的试验一致。进行肿瘤基因组(WES和/或靶向NGS组)、转录组(RNAseq)和组织微环境成像以及粪便宏基因组测序。肿瘤基因集富集分析鉴定出多个基于免疫的转录组程序,以区分生存期较长和较短的患者(p≤0.01)。GBM免疫富集与治疗前肿瘤间充质亚型和患者胃肠道细菌分类群高度相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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.

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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
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.
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