Lower Airway Dysbiosis Affects Lung Cancer Progression

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and 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...

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Bibliographic Details
Published inCancer discovery Vol. 11; no. 2; pp. 293 - 307
Main Authors Tsay, Jun-Chieh J., Wu, Benjamin G., Sulaiman, Imran, Gershner, Katherine, Schluger, Rosemary, Li, Yonghua, Yie, Ting-An, Meyn, Peter, Olsen, Evan, Perez, Luisannay, Franca, Brendan, Carpenito, Joseph, Iizumi, Tadasu, El-Ashmawy, Mariam, Badri, Michelle, Morton, James T., Shen, Nan, He, Linchen, Michaud, Gaetane, Rafeq, Samaan, Bessich, Jamie L., Smith, Robert L., Sauthoff, Harald, Felner, Kevin, Pillai, Ray, Zavitsanou, Anastasia-Maria, Koralov, Sergei B., Mezzano, Valeria, Loomis, Cynthia A., Moreira, Andre L., Moore, William, Tsirigos, Aristotelis, Heguy, Adriana, Rom, William N., Sterman, Daniel H., Pass, Harvey I., Clemente, Jose C., Li, Huilin, Bonneau, Richard, Wong, Kwok-Kin, Papagiannakopoulos, Thales, Segal, Leopoldo N.
Format Journal Article
LanguageEnglish
Published United States 01.02.2021
Subjects
Adenocarcinoma - complications
Adenocarcinoma - microbiology
Adenocarcinoma - mortality
Adenocarcinoma - secondary
Animals
Cohort Studies
Disease Models, Animal
Disease Progression
Dysbiosis - complications
Female
Humans
Lung Neoplasms - complications
Lung Neoplasms - microbiology
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Mice
Mice, Transgenic
Microbiota
Neoplasm Metastasis
Neoplasm Staging
New York
Proportional Hazards Models
Survival Analysis
New York
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Summary:In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and 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 as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with 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. . .
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Authors Contributions
JC.J.T. and L.N.S. conceived of and designed the study. Data was obtained by JC.J.T., B.G.W, I.S., K.G., R.S., Y.L., T.A.Y., P.M., E.O., L.P., B.F., J.C., T.I., M.E., M.H.B, J.M, N.S., L.H, W.M. J.C.C., H.L, R.B, R.P., A.Z., V. M., led by L.N.S. Data were analyzed by JC.J.T., B.G.W, I.S., K.G., M.H.B, J.M, N.S., L.H, W.M. J.C.C., H.L, R.B., R.P., S.B.K., C.A.L led by L.N.S. The first draft of the manuscript was written by JC.J.T. and L.N.S. All authors read, critically revised and approved the final manuscript.
ISSN:2159-8274
2159-8290
2159-8290
DOI:10.1158/2159-8290.CD-20-0263