• Tumor microbiome-transcriptome...

*Result*: Tumor microbiome-transcriptome crosstalk identifies Prevotella as an immunotherapeutic predictor in NSCLC.

Title:
Tumor microbiome-transcriptome crosstalk identifies Prevotella as an immunotherapeutic predictor in NSCLC.
Authors:
Wang N; Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, China., Ma L; Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China., Huang Y; Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China., Zhou X; College of Informatics, Huazhong Agricultural University, Wuhan 430070, China., Rong Y; Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China., Long F; Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China., Qiu W; College of Informatics, Huazhong Agricultural University, Wuhan 430070, China., Wu S; Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China., Hu Y; Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China., He X; Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China., He J; Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China., Tian S; Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China., Hu W; Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China., Yuan C; Department of Laboratory Medicine, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430016, China., Wang F; Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, China.; Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.; Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan 430071, China.
Source:
Theranostics [Theranostics] 2026 Jan 01; Vol. 16 (7), pp. 3426-3446. Date of Electronic Publication: 2026 Jan 01 (Print Publication: 2026).
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101552395 Publication Model: eCollection Cited Medium: Internet ISSN: 1838-7640 (Electronic) Linking ISSN: 18387640 NLM ISO Abbreviation: Theranostics Subsets: MEDLINE
Imprint Name(s):
Original Publication: Wyoming, N.S.W. : Ivyspring International Publisher, 2011-
MeSH Terms:
Carcinoma, Non-Small-Cell Lung*/microbiology , Carcinoma, Non-Small-Cell Lung*/immunology , Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/therapy , Lung Neoplasms*/microbiology , Lung Neoplasms*/immunology , Lung Neoplasms*/genetics , Lung Neoplasms*/drug therapy , Lung Neoplasms*/therapy , Microbiota*/immunology , Microbiota*/genetics , Prevotella*/isolation & purification , Prevotella*/immunology , Prevotella*/genetics , Transcriptome*, Tumor Microenvironment/immunology ; Tumor Microenvironment/genetics ; Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use ; Immune Checkpoint Inhibitors/pharmacology ; ErbB Receptors/antagonists & inhibitors ; Humans ; Prognosis ; Female ; Male ; Middle Aged ; Aged
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Contributed Indexing:
Keywords: NSCLC; Prevotella; immunotherapy response; microbiome; transcriptome
Substance Nomenclature:
0 (Immune Checkpoint Inhibitors)
EC 2.7.10.1 (ErbB Receptors)
Entry Date(s):
Date Created: 20260129 Date Completed: 20260129 Latest Revision: 20260131
Update Code:
20260131
PubMed Central ID:
PMC12846730
DOI:
10.7150/thno.126091
PMID:
41608560
Database:
MEDLINE

*Further Information*

*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<sup>+</sup> 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 public datasets. Furthermore, a combined diagnostic model integrating PT-resident Prevotella abundance with routine clinical blood indicators demonstrated markedly superior predictive performance for ICI response compared with the conventional biomarker PD-L1. By contrast, PT-resident Prevotella exhibited no association with treatment response in the EGFR-targeted therapy cohort. Conclusion: PT-resident Prevotella is strongly associated with the prognosis and ICI response in patients with NSCLC. Moreover, integration of PT-resident Prevotella with routine clinical blood indicators holds promise as a potential auxiliary diagnostic tool to facilitate personalized immunotherapy in NSCLC.
(© The author(s).)*

*Competing Interests: The authors have declared that no competing interest exists.*