Project description:Lung cancer is closely associated with chronic inflammation, but the mechanism underlying such inflammation has not been clearly defined. The lung is a mucosal tissue colonized by a diverse bacterial community at the steady state, and pulmonary infections commonly present in lung cancer patients are linked to clinical outcomes. Here we provide evidence that local microbiota provoke inflammation associated with lung adenocarcinoma by activating lung-resident gamma-delta T cells. Germ-free or antibiotic-treated mice were significantly protected from lung tumor initiation and progression induced by Kras mutation and p53 loss. Mechanistically, commensal bacteria stimulated My88-dependent IL-1beta and IL-23 production from myeloid cells, inducing proliferation and activation of Vγ6+Vδ1+ γδ T cells that produced IL-17 and other effector molecules to promote inflammation and tumor cell proliferation. Our findings provide a clear link between local microbiota-immune crosstalk and lung tumorigenesis, and thereby define key cellular and molecular mediators that may serve as effective targets in lung cancer treatment and prevention.
Project description:Genome wide DNA methylation profiling of normal lung tissue samples. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in nor mal lung tissue samples. Samples included 244 normal lung tissue samples from lung cancer patients. Environment and Genetics in Lung Cancer Etiology EAGLE; Population-based case-control study Bisulphite converted DNA from 244 fresh-frozen primary human lung samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2. This file has 60 samples.
Project description:The subject is to study the lung microbiota and the one of upper airways (UAs) (much less studied than the intestinal microbiota) in 40 patients having lung cancer. 20 patients undergo only surgical treatment, while other half receives also chemotherapy. The idea is to explore changes in microbiota of the lung, upper UAs and intestine, and potentially find associations between them. These results will serve us as a base for the future study, focused on manipulation of the microbiota by prebiotics, probiotics or symbiotics and its effect on anti-cancer treatment tolerance and effectiveness.