Research News

In studies of the environment in and around tumors, scientists have found mini-immune systems, blood vessels, connective tissues and, in some cases, entire communities of bacteria, viruses and fungi. This community of microbes is called the “tumor microbiome,” and the term is only a few years old. 

Cleveland Clinic is already working to move the field past identifying which microbes are present in a tumor to understanding what those microbes are actually doing, says J. Mark Brown, PhD, Director of Research for Cleveland Clinic’s Center for Microbiome & Human Health. Many of Cleveland Clinic’s functional tumor microbiome studies ask whether changing the microbes in the tumor microbiome can change how cancers behave and respond to treatment.  

Their findings could influence new treatments designed to modify the tumor microbiome, aiming to prevent anti-tumor immunity, as well as how well a tumor responds to – or resists – treatment. 

What is the tumor microbiome? 

The tumor microbiome, sometimes called the “oncobiome,” is the community of bacteria, viruses, fungi and other microorganisms that live in and around tumors. The microbes can live on the surface of the tumor, inside the tissue between cells, or even inside the cancer cells themselves. Every tumor microbiome is different. Some tumors support very few microbes, while others harbor thriving communities. Natalie Silver, MD, MS, even says that two tumors that look identical under a microscope could have completely different bacterial communities.  

"The tumor microbiome has always been there. The challenge is that studying it requires exceptional care and multiple complimentary approaches,” says Dr. Silver, a surgical oncologist whose laboratory studies the tumor microbiome in head and neck cancers. “This work is critical to understanding cancer progression and treatment, and treatment response – otherwise, we risk overlooking a huge part of the story.”

How does the tumor microbiome impact cancer progression and care? 

The effect a tumor microbiome has on cancer seems to depend on many factors, including the type of cancer, where the tumor develops and what microbes are present. 

Cleveland Clinic researchers have shown just how context-dependent the tumor microbiome and its effects can be. In breast tumors, researchers led by Ying Ni, PhD, and the late Charis Eng, MD, PhD, saw that higher levels of S. aureus were linked to increased immune activity and survival. In head and neck squamous cell carcinoma, however, Dr. Silver and her collaborators have linked high levels to decreased immune activity and poor treatment responses. 

Dr. Silver says that the future of microbiome-based cancer care will depend on understanding when microbes are helping and when they are hurting. In some cancers, bacteria are promising therapeutic targets. In others, they are more promising as biomarkers. 

"There is no one-size-fits-all approach to the tumor microbiome, because bacteria can either stimulate or suppress the immune system, depending on context," Dr. Silver says. “The same is true of cancer care: not every patient or tumor warrants the same approach.” 

Some researchers are adding genetically engineered bacteria to ovarian and breast tumors to stimulate the immune response while others, like Dr. Silver, are using antibiotics to remove bacteria from head and neck tumors. Early results are promising for both cancer types. 

"When a field is still relatively new, you have to look beyond your own area of expertise and learn from people who approach the problem differently," Dr. Silver says. "By bringing together doctors and scientists from related disciplines, we’re figuring out how microbes shape cancer biology in ways we could not fully explore just a decade ago."