Lower Airway Dysbiosis Affects Lung Cancer Progression
Abstract
In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB–IV tumor–node–metastasis lung cancer group and is associated with poor prognosis, as shown by decreased survival among subjects with early-stage disease (I–IIIA) and worse tumor progression as measured by RECIST scores among subjects with stage IIIB–IV disease. In addition, this lower airway microbiota signature was associated with upregulation of the IL17, PI3K, MAPK, and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL17 inflammatory phenotype, and activation of checkpoint inhibitor markers.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 01, 2021
- Source ID
- 10.1158/2159-8290.cd-20-0263
Entities
People
- Adriana Heguy
- Anastasia-maria Zavitsanou
- Andre L. Moreira
- Aristotelis Tsirigos
- Benjamin G. Wu
- Brendan Franca
- Cynthia A. Loomis
- Daniel Sterman
- Evan Olsen
- Gaetane Michaud
- Harald Sauthoff
- Harvey I Pass
- Huilin Li
- Imran Sulaiman
- James T. Morton
- Jamie L. Bessich
- Jose C. Clemente
- Joseph Carpenito
- Jun-chieh J. Tsay
- Katherine Gershner
- Kevin Felner
- Kwok-kin Wong
- Leopoldo Naman Segal
- Linchen He
- Luisannay Perez
- Mariam El-ashmawy
- Michelle Badri
- Nan Shen
- Peter Meyn
- Ray Pillai
- Richard Bonneau
- Robert L. Smith
- Rosemary Schluger
- Samaan Rafeq
- Sergei B Koralov
- Tadasu Iizumi
- Thales Papagiannakopoulos
- Ting-an Yie
- Valeria Mezzano
- William Moore
- William N. Rom
- Yonghua Li
Organizations
- Flatiron Institute
- Grossman School of Medicine
- Icahn School of Medicine at Mount Sinai
- Indiana Clinical and Translational Sciences Institute
- National Institutes of Health
- New York University
- United States Department of Defense
- United States Department of Veterans Affairs
- Wake Forest School of Medicine