期刊
CANCER DISCOVERY
卷 11, 期 2, 页码 293-307出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-20-0263
关键词
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类别
资金
- PACT grant
- EDRN [5U01CA086137-13]
- DoD [W81XWH-16-1-0324]
- 2018 AACR-Johnson and Johnson Lung Cancer Innovation Science Grant [18-90-52-ZHAN]
- A Breath of Hope Foundation
- Simons Foundation
- CTSI [UL1 TR000038]
- Laura and Isaac Perlmutter Cancer Center [P30CA016087]
- FAMRI Young Clinical Scientist Award
- Stony Wold-Herbert Fund Grant-in-Aid/Fellowship
- AbbVie Inc.
- Amgen Inc.
- Boehringer-Ingelheim Pharma GmbH and Co. KG
- Bristol-Myers Squibb
- Celgene Corporation
- Genentech Inc.
- Gilead
- GlaxoSmithKline plc
- Janssen Pharmaceutical Companies of Johnson and Johnson
- Novartis Institutes for Biomedical Research
- Pfizer Inc.
- Sanofi
- [R37 CA244775]
- [K23 AI102970]
- [T32 CA193111]
- [UL1TR001445]
- [R01 HL125816]
- [R01 DK110014]
- [S10 OD021747]
In lung cancer patients, dysbiosis of the lower airway microbiota is more prevalent in advanced stages and associated with poor prognosis, upregulation of IL17, PI3K pathways, etc. in the airway transcriptome. The dysbiosis with V. parvula in the lower airway of the KP lung cancer model leads to decreased survival and tumor progression.
In lung cancer, enrichment of the lower airway microbiota with oral com- mensals 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-nodemetastasis 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 Veittorrella parvuto 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. SIGNINCANCE: 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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