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.