Tumor microbiome-transcriptome crosstalk identifies Prevotella as an immunotherapeutic predictor in NSCLC

作者：Na Wang, Lifang Ma, Yugang Huang, Xionghui Zhou, Yuan Rong, Fei Long, Wanbo Qiu, Si Wu, Yue Hu, Xin He, Jia He, Sufang Tian, Weidong Hu, Chunhui Yuan, Fubing Wang · 发表于：Theranostics · 年份：2026 · DOI：10.7150/thno.126091 · 被引用次数：2 · 研究领域：Cancer Immunotherapy and Biomarkers、Gut microbiota and health、Immune cells in cancer

Background: The tumor-resident microbiome plays a pivotal role in shaping the tumor immune microenvironment; however, its relationship with the host transcriptome and the response to immune checkpoint inhibitors (ICIs) remains largely uncharacterized in non-small cell lung cancer (NSCLC).This study aimed to elucidate the relationship between tissue-resident microbiota, host transcriptomic alterations, and immunotherapy response in NSCLC.Methods: Paired tumor (T) and paracancerous tissue (PT) samples from patients with NSCLC were analyzed using 2bRAD-M and bulk RNA sequencing to generate comprehensive microbiome and transcriptome profiles.The conditional mutual information algorithm was employed to systematically investigate intratumoral microbe-host interactions.Associations between key microbes and patient prognosis, ICI response, and response to epidermal growth factor receptor (EGFR)-targeted therapy were assessed across four independent local clinical cohorts.Results: Higher microbial richness, α-diversity, and β-diversity were observed in PT samples than in T samples.Specifically, PT-resident Bradyrhizobium and Prevotella were identified as key bacterial taxa significantly associated with immune cell populations, including CD8 + T cells, natural killer cells, and activated dendritic cells.Among these, PT-resident Prevotella, but not Bradyrhizobium, was independently associated with improved prognosis of patients with NSCLC and ICI response in both local clinical sets and...