PHILANTHROPY SPOTLIGHT

Supporting Discovery in the Lung Microbiome

A CHEST Research Grant allowed Jun-Chieh James Tsay, MD, to challenge conventional thinking about lung cancer development and treatment

By Andrea Brown
July 7, 2026 | VOLUME 4, ISSUE 2

For much of his career, Jun-Chieh James Tsay, MD, has been focused on a fundamental part of lung cancer care: How can clinicians detect the disease earlier and better understand why some patients respond to treatment while others do not?

As a pulmonologist and researcher at NYU Langone Health, Dr. Tsay began his research career studying lung cancer screening under the mentorship of physicians who were investigating screening methods years before they became part of standard clinical practice.

Jun-Chieh James Tsay, MD
Director, NYU Langone Lung Cancer Biomarker Program

“We always knew smoking was the biggest risk factor for lung cancer,” Dr. Tsay said. “But I became interested in how we could detect cancer earlier and whether there were different ways to identify patients at risk or better understand the disease.”

That curiosity eventually led him to a research area that, at the time, received relatively little attention: the lung microbiome.

Supported by the 2019 CHEST Research Grant in Lung Cancer, Dr. Tsay set out to investigate whether bacteria living in the lower airways could influence inflammation and lung cancer progression. The project would ultimately contribute to research published in Cancer Discovery and help establish a new direction for future lung cancer studies.

A new frontier in lung cancer research

When discussions about the microbiome began gaining traction in cancer research, most of the attention was focused on the gut. Scientists were uncovering evidence that the trillions of microorganisms living in the digestive tract could influence immune function, cancer progression, and even responses to treatment.

For researchers studying lung cancer, however, an important question remained unanswered: Could the microbiome inside the lungs play a similar role?

At the time, the idea was far from mainstream.

“I became interested in how we could detect cancer earlier and whether there were different ways to identify patients at risk or better understand the disease.”

“Traditionally, people thought the lungs were sterile,” Dr. Tsay said. “The assumption was that if bacteria were present, it meant infection. What we were finding, however, was that the lungs are not completely sterile. There are microbes present at very low levels, and the body is constantly working to clear them.”

That realization opened the door to an entirely new area of investigation.

Dr. Tsay and his team became interested in understanding whether microbes in the lower airways could trigger inflammatory pathways associated with lung cancer. Specifically, the CHEST-funded project focused on inflammasomes and interleukin-1β—components of the immune system that help regulate inflammatory responses.

While inflammation is a critical part of the body’s defense system, chronic inflammation can have unintended consequences. In the setting of cancer, persistent inflammation may create an environment that allows tumors to grow, spread, and evade immune defenses.

“We wanted to understand whether there was a specific mechanism connecting the lung microbiome and inflammatory pathways,” Dr. Tsay said. “If bacteria in the lungs were influencing those pathways, it could help explain some of what we see in lung cancer progression.”

Connecting bacteria and lung cancer

The team’s research focused on patients with non-small cell lung cancer (NSCLC), the most common form of lung cancer. What they discovered was both surprising and significant.

They found that certain bacteria commonly detected in the mouth were appearing in the lower airways of some patients. More importantly, those bacterial patterns were associated with worse clinical outcomes.

According to the study, patients whose lower airway microbiome contained oral bacteria experienced poorer survival outcomes than patients whose lung microbiome contained different bacterial profiles.

“A lot of people experience what we call silent aspiration,” Dr. Tsay said. “Small amounts of bacteria from the mouth can enter the lungs. Most people are able to clear those bacteria without any issue. But if those bacteria persist, they may contribute to chronic inflammation.”

“If bacteria in the lungs were influencing those pathways, it could help explain some of what we see in lung cancer progression.”

To understand why, the team examined how these microbes interacted with the immune system. The study showed that lower airway dysbiosis—an imbalance in the lung’s microbial community—was associated with increased inflammatory signaling and changes in the tumor microenvironment. The research identified activation of pathways involving interleukin-17, extracellular signal-regulated kinase, vascular endothelial growth factor, and inflammasome signaling, all of which have been associated with cancer progression.

To strengthen their findings, the team conducted experiments in mouse models and observed similar results. The results suggested that bacteria from the mouth may contribute to a pro-inflammatory environment in the lungs that supports tumor growth and progression.

“Being able to reproduce what we observed in patients within a preclinical model was incredibly important,” Dr. Tsay said. “It gave us greater confidence that this wasn’t simply an association and that these microbial communities may be actively influencing disease processes.”

Why the findings matter

Although the research is still in its early stages, its implications extend beyond understanding the biology of lung cancer.

One of the most important questions cancer researchers face today is why some patients respond exceptionally well to treatment while others do not. Over the past decade, immunotherapy has transformed the treatment landscape for many patients with lung cancer. Yet significant variability remains in how patients respond.

“There have been tremendous advances in treatment,” Dr. Tsay said. “The challenge is that these therapies don’t work for everyone. One of our goals is to understand why certain patients benefit while others don’t.”

Researchers increasingly believe the microbiome may be part of that answer. Studies involving the gut microbiome have already demonstrated that microbial communities can influence responses to immunotherapy. And Dr. Tsay said he believes the lung microbiome may provide similar insights for patients with lung cancer.

“The challenge is that these therapies don’t work for everyone. One of our goals is to understand why certain patients benefit while others don’t.”

The next area of discovery

That question—why some patients respond to treatment while others don’t—is now driving the next phase of Dr. Tsay’s research. After identifying links between the lung microbiome, inflammation, and lung cancer progression, Dr. Tsay and his colleagues expanded their work to study how microbial communities may influence responses to immunotherapy.

The team also secured additional collaborative funding from the National Institutes of Health on research examining the relationship between the microbiome and immunotherapy outcomes. More recently, Dr. Tsay’s research has shifted toward another area he believes has been overlooked: lymph nodes within the lungs.

Traditionally viewed as sites where cancer spreads, lymph nodes also serve as critical hubs of immune activity.

“That’s where many of the immune interactions are happening,” he said. “We want to understand how the immune system is functioning within that environment and how those responses change as cancer progresses or patients receive treatment.”

“These types of grants are incredibly important for researchers who are just starting out.”

How CHEST helped launch the research

The grant from CHEST arrived at a pivotal point in Dr. Tsay’s career.

At the time, he was still establishing himself as an independent investigator. Like many early career researchers, he needed preliminary funding to collect data, explore new ideas, and build the foundation necessary to pursue larger grants.

“These types of grants are incredibly important for researchers who are just starting out,” he said. “They give you the opportunity to generate preliminary data, develop new research directions, and build the evidence needed to apply for larger federal funding opportunities.”

Beyond the financial support, receiving the grant provided validation for a research area that many scientists had not yet begun to explore.

“This was a high-risk area because there wasn’t much data available,” Dr. Tsay said. “But that’s also what made it exciting. We felt there was an opportunity to learn something important that could open the door to future discoveries.”

Support CHEST grants like this

Through clinical research grants, CHEST assists in acquiring vital data and clinically important results that can advance medical care. You can help support projects like this by making a gift to CHEST.

MAKE A GIFT » | LEARN ABOUT CHEST PHILANTHROPY »