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With one of the world’s largest human cohorts involved in translational lung cancer investigations, �ٺ���Ƶ Health investigators are building a research program to identify organisms native to an individual’s lung microbiome that can influence the predisposition, natural progress, and outcome of lung cancer.

A Long History of Microbiome Discovery, Starting with the Gut

The idea that bacteria and other foreign organisms can influence a condition’s course and outcome is not a new concept at �ٺ���Ƶ. Noted physician and researcher Martin J. Blaser, MD, who served until recently as the chair of the , has studied the human microbiome for more than 20 years. He was one of the first to demonstrate the importance of Helicobacter pylori in the gut on the modulation of the host immune tone with relevance for multiple disease processes, such as gastric cancer and inflammatory airway diseases. To build on this discovery, �ٺ���Ƶ’s Human Microbiome Program was created in 2013 as a translational research program focused on microbial–host interaction using sequencing methods applied to human samples to investigate microbial composition and function.

Making the Leap from Gut to Lungs

Translating the insights about the human gut microbiome to the lungs, investigators at �ٺ���Ƶ have discovered that certain bacteria in the airway can signal that a patient is at risk for lung cancer.

“Airway flora of different types of organisms seem to be much different between patients at high risk and patients who have lung cancer, compared with those at low risk,” says Harvey I. Pass, MD, the Stephen E. Banner Professor of Thoracic Oncology, director of the , and surgical chief of thoracic oncology at Perlmutter Cancer Center at �ٺ���Ƶ.

The first published reports making this connection in humans were produced by �ٺ���Ƶ researchers Jun-Chieh J. Tsay, MD, and Leopoldo N. Segal, MD. By collecting a large number of samples via bronchoscopy and analyzing their bacterial content, the investigators have been able to identify relationships between lung microbiomes and human disease states. In addition, in soon-to-be-published animal studies, they have shown the influence of the microbiome in the airway on T cells, other types of immune cells, and—ultimately—on the course of lung cancer.

Closer to Home: The Tumor Microenvironment

Not only do human lungs have their own microbiomes, but tumors themselves are home to unique microenvironments of immune cells and nonimmune cells—the focus of another line of research at the center.

“We want to better understand how the microbiomes of lungs and of tumors relate to and interact with each other,” says Dr. Pass.

To answer that question, researchers have to work with a sterile tumor. But once a tumor is removed from its host, it is no longer sterile. So surgeons at �ٺ���Ƶ devised a method to save just-resected tumors in sterile vials at the operating table. The vials are snap-frozen and stored until an experiment is conducted.

“This takes a tremendous amount of effort,” notes Dr. Pass. “The surgeon has to remove the tissue, cut it, and ensure it remains sterile, and then we have to commit to storing it. Undertaking this level of commitment, and following through with studies of snap-frozen tumors, is what makes �ٺ���Ƶ a world leader,” he says.

To date, researchers have examined snap-frozen tumors from 150 patients to try to predict the correlation between patients’ microbiomes, rates of cancer recurrence, and immune system function. They have identified a lung microbiota signature associated with a poorer prognosis: in early stage lung cancer patients undergoing cardiothoracic surgery, they found that the microbial DNA in the excised tumor and in the healthy lung can predict cancer recurrence.

“We postulate that the microbes present in the lower airways affect patients’ ability to mount an effective immune surveillance, thereby limiting their ability to prevent tumor transformation,” says Dr. Segal, assistant professor of medicine and the lead investigator in �ٺ���Ƶ’s Lung Microbiome Program.

�ٺ���Ƶ is currently under consideration for a SPORE (Specialized Programs of Research Excellence) grant from the National Cancer Institute to deepen the investigation into this relationship.