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 Discovjournal_title
Cancer discoveryauthors
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,Feldoi
10.1158/2159-8290.CD-20-0263subject
Has Abstractpub_date
2020-11-11 00:00:00eissn
2159-8274issn
2159-8290pii
2159-8290.CD-20-0263pub_type
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