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. 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.See related commentary by Zitvogel and Kroemer, p. 224.This article is highlighted in the In This Issue feature, p. 211.

journal_name

Cancer Discov

journal_title

Cancer discovery

authors

Tsay JJ,Wu BG,Sulaiman I,Gershner K,Schluger R,Li Y,Yie TA,Meyn P,Olsen E,Perez L,Franca B,Carpenito J,Iizumi T,El-Ashmawy M,Badri M,Morton JT,Shen N,He L,Michaud G,Rafeq S,Bessich JL,Smith RL,Sauthoff H,Fel

doi

10.1158/2159-8290.CD-20-0263

subject

Has Abstract

pub_date

2020-11-11 00:00:00

eissn

2159-8274

issn

2159-8290

pii

2159-8290.CD-20-0263

pub_type

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