Lower airway dysbiosis affects lung cancer progression

Jun Chieh J. Tsay, Benjamin G. Wu, Imran Sulaiman, Katherine Gershner, Rosemary Schluger, Yonghua Li, Ting An Yie, Peter Meyn, Evan Olsen, Luisannay Perez, Brendan Franca, Joseph Carpenito, Tadasu Iizumi, Mariam El-Ashmawy, Michelle Badri, James T. Morton, Nan Shen, Linchen He, Gaetane Michaud, Samaan RafeqJamie L. Bessich, Robert L. Smith, Harald Sauthoff, Kevin Felner, Ray Pillai, Anastasia Maria Zavitsanou, Sergei B. Koralov, Valeria Mezzano, Cynthia A. Loomis, Andre L. Moreira, William Moore, Aristotelis Tsirigos, Adriana Heguy, William N. Rom, Daniel H. Sterman, Harvey I. Pass, Jose C. Clemente, Huilin Li, Richard Bonneau, Kwok Kin Wong, Thales Papagiannakopoulos, Leopoldo N. Segal

Research output: Contribution to journalArticlepeer-review

Abstract

In lung cancer, enrichment of the lower airway microbiota with oral com-mensals 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 micro-biota 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. SIGnIFICAnCE: Multiple lines of investigation have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here, we support that the local airway microbiota modulates the host immune tone in lung cancer, affecting tumor progression and prognosis.

Original languageEnglish (US)
Pages (from-to)293-307
Number of pages15
JournalCancer Discovery
Volume11
Issue number2
DOIs
StatePublished - Feb 2021

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Lower airway dysbiosis affects lung cancer progression'. Together they form a unique fingerprint.

Cite this