Lung commensal bacteria promote lung cancer progression through NK cell-mediated immunosuppressive microenvironment

Symbiotic microbiota pervades the majority of the human body's organs and tissues, functioning as crucial regulators of both health maintenance and disease progression. Pertinently, lung adenocarcinoma has been indisputably linked to chronic inflammation. However, the precipitators that instigate such inflammation, along with the particular immune mediators involved, remain enigmatic and warrant extensive exploration. This research revealed a significant variance exists in the commensal bacteria between lung cancer tissues and their normal counterparts. This holds true for both clinical patients and mice, where both the diversity and abundance of bacteria in tumor tissues significantly surpass those in normal tissues. It has been demonstrated that disturbances in pulmonary commensal bacteria can stimulate the proliferation of tumor cells. Mechanistically, we suggest that lung bacteria may promote the expression of the NK cell immunosuppressive molecule TIGIT along with the secretion of IL-2 and IFN-γ. This consequently mediates alterations in the immunosuppressive microenvironment, thereby fostering tumor proliferation.