@article{cc3ee5459dce4754879283804ca6753a,
title = "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. ",
keywords = "Adenocarcinoma/complications, Animals, Cohort Studies, Disease Models, Animal, Disease Progression, Dysbiosis/complications, Female, Humans, Lung Neoplasms/complications, Mice, Mice, Transgenic, Microbiota, Neoplasm Metastasis, Neoplasm Staging, New York, Proportional Hazards Models, Survival Analysis",
author = "Tsay, {Jun Chieh J.} and Wu, {Benjamin G.} and Imran Sulaiman and Katherine Gershner and Rosemary Schluger and Yonghua Li and Yie, {Ting An} and Peter Meyn and Evan Olsen and Luisannay Perez and Brendan Franca and Joseph Carpenito and Tadasu Iizumi and Mariam El-Ashmawy and Michelle Badri and Morton, {James T.} and Nan Shen and Linchen He and Gaetane Michaud and Samaan Rafeq and Bessich, {Jamie L.} and Smith, {Robert L.} and Harald Sauthoff and Kevin Felner and Ray Pillai and Zavitsanou, {Anastasia Maria} and Koralov, {Sergei B.} and Valeria Mezzano and Loomis, {Cynthia A.} and Moreira, {Andre L.} and William Moore and Aristotelis Tsirigos and Adriana Heguy and Rom, {William N.} and Sterman, {Daniel H.} and Pass, {Harvey I.} and Clemente, {Jose C.} and Huilin Li and Richard Bonneau and Wong, {Kwok Kin} and Thales Papagiannakopoulos and Segal, {Leopoldo N.}",
note = "Funding Information: This study was supported by R37 CA244775 (L.N. Segal, NIH/NCI); PACT grant (L.N. Segal, FNIH); K23 AI102970 (L.N. Segal, NIH/NIAD); EDRN 5U01CA086137-13 (W.N. Rom); DoD W81XWH-16-1-0324 (J.-C.J. Tsay); the 2018 AACR?Johnson and Johnson Lung Cancer Inno-vation Science Grant Number 18-90-52-ZHAN (H.I. Pass/L.N. Segal); A Breath of Hope Foundation (J.-C.J. Tsay); Simons Foundation (R. Bonneau); and CTSI Grant #UL1 TR000038 (L.N. Segal). The Genome Technology Center and ExpPath Core are partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center (A. Heguy and A. Tsirigos); T32 CA193111 (B.G. Wu); UL1TR001445 (B.G. Wu); FAMRI Young Clinical Scientist Award (B.G. Wu); Stony Wold-Herbert Fund Grant-in-Aid/Fellowship (B.G. Wu, I. Sulaiman, and K. Gershner); R01 HL125816 (L.N. Segal and S.B. Koralov, NIH/NHLBI); and R01 DK110014 (H. Li and L. He). We would like to thank the Genome Technology Center (GTC) for expert library preparation and sequencing, the Applied Bioinformatics Laboratories (ABL) for providing bioinformatics support and helping with the analysis and interpretation of the data, and Experimental Pathology Research Laboratory for histopathology services and imaging. GTC, ExpPath Core, and ABL are shared resources partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center. This work has used com- puting resources at the NYU School of Medicine High Performance Computing Facility. Financial support for the PACT project is possible through funding support provided to the FNIH by AbbVie Inc., Amgen Inc., Boehringer-Ingelheim Pharma GmbH and Co. KG, Bristol-Myers Squibb, Celgene Corporation, Genentech Inc., Gilead, GlaxoSmith-Kline plc, Janssen Pharmaceutical Companies of Johnson and Johnson, Novartis Institutes for Biomedical Research, Pfizer Inc., Sanofi, and Shared Instrumentation Grant S10 OD021747 award for the Vectra Imaging system in Experimental Pathology. Funding Information: J. Carpenito reports grants from NIH during the conduct of the study. J. Pass reports grants from NCI EDRN U01 and AACR/J&J Grant during the conduct of the study. K.-K. Wong reports being a founder and equity holder of G1 Therapeutics. K.-K. Wong has sponsored research agreements with Pfizer, Janssen, Takeda, Targimmune, AstraZeneca, Novartis, Merck, Ono, and Array. L. Segal reports grants from NCI/NIH, FNIH, and AACR Grant during the conduct of the study. No disclosures were reported by the other authors. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2021",
month = feb,
doi = "10.1158/2159-8290.CD-20-0263",
language = "English (US)",
volume = "11",
pages = "293--307",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "2",
}