Microbiota-immune interaction in lung cancer

Dr. Chengcheng Jin
 
Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology
 

Abstract: 
 
Lung cancer is closely associated with chronic inflammation, but the causes of inflammation and the specific immune mediators have not been fully elucidated. The lung is a mucosal tissue colonized by a diverse bacterial community, and pulmonary infections commonly present in lung cancer patients are linked to clinical outcomes. Here we provide evidence that local microbiota provoke inflammation and lung cancer development by activating lung-resident γδ T cells. Mechanistically, we showed that lung tumor growth is associated with increased bacterial load and altered bacterial composition in the airway. This dysregulated local microbiota stimulated proliferation and activation of lung-resident Vγ6+Vδ1+ γδ T cells. These γδ T cells then produced IL-17 to promote neutrophil infiltration and inflammation in the tumor microenvironment; they also expressed IL-22, amphiregulin and other effector molecules to directly enhance tumor cell proliferation. This study provides the first evidence clearly linking local microbiota-immune crosstalk to lung tumorigenesis, and thereby not only define novel targets for cancer prevention and treatment, but also open up new avenues for future research. We are currently combining single cell RNA-seq, multiplex IF/FISH and advanced CRISPRcas9 in vivo gene-editing tools to further interrogate the interactions between microbiota, host immune system and tumor cells in lung cancer.
 
 
Time: 14:00-15:30, August 26th (Monday)

Venue: Room D326, Medical Science Building

Host: Dr. Chen Dong