Lower Airway Dysbiosis Affects Lung Cancer Progression.

Autor:	Tsay JJ; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York.; Division of Pulmonary and Critical Care Medicine, VA New York Harbor Healthcare System, New York, New York., Wu BG; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York.; Division of Pulmonary and Critical Care Medicine, VA New York Harbor Healthcare System, New York, New York., Sulaiman I; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Gershner K; Section of Pulmonary, Critical Care, Allergy and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina., Schluger R; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Li Y; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Yie TA; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Meyn P; NYU Langone Genomic Technology Center, New York University School of Medicine, New York, New York., Olsen E; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Perez L; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Franca B; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Carpenito J; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Iizumi T; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., El-Ashmawy M; Department of Medicine, New York University School of Medicine, New York, New York., Badri M; Department of Biology, New York University, New York, New York., Morton JT; Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, New York., Shen N; Department of Genetics and Genomic Sciences and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York., He L; Department of Population Health, New York University School of Medicine, New York, New York., Michaud G; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Rafeq S; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Bessich JL; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Smith RL; Division of Pulmonary and Critical Care Medicine, VA New York Harbor Healthcare System, New York, New York., Sauthoff H; Division of Pulmonary and Critical Care Medicine, VA New York Harbor Healthcare System, New York, New York., Felner K; Division of Pulmonary and Critical Care Medicine, VA New York Harbor Healthcare System, New York, New York., Pillai R; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Zavitsanou AM; Department of Pathology, New York University School of Medicine, New York, New York., Koralov SB; Department of Pathology, New York University School of Medicine, New York, New York., Mezzano V; Department of Pathology, New York University School of Medicine, New York, New York., Loomis CA; Department of Pathology, New York University School of Medicine, New York, New York., Moreira AL; Department of Pathology, New York University School of Medicine, New York, New York., Moore W; Department of Radiology, New York University School of Medicine, New York, New York., Tsirigos A; Department of Pathology, New York University School of Medicine, New York, New York., Heguy A; NYU Langone Genomic Technology Center, New York University School of Medicine, New York, New York.; Department of Pathology, New York University School of Medicine, New York, New York., Rom WN; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Sterman DH; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York., Pass HI; Department of Cardiothoracic Surgery, New York University School of Medicine, New York, New York., Clemente JC; Department of Genetics and Genomic Sciences and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Li H; Department of Population Health, New York University School of Medicine, New York, New York., Bonneau R; Department of Biology, New York University, New York, New York.; Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, New York.; Center for Data Science, New York University School of Medicine, New York, New York., Wong KK; Division of Hematology and Oncology, New York University School of Medicine, New York, New York., Papagiannakopoulos T; Department of Pathology, New York University School of Medicine, New York, New York., Segal LN; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York. Leopoldo.Segal@nyumc.org.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2021 Feb; Vol. 11 (2), pp. 293-307. Date of Electronic Publication: 2020 Nov 11.
DOI:	10.1158/2159-8290.CD-20-0263
Abstrakt:	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 . (©2020 American Association for Cancer Research.)
Databáze:	MEDLINE
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