Cleveland Clinic researchers have identified a link between high levels of bacteria in cancerous tumors and resistance to immunotherapy treatments in patients with head and neck squamous cell carcinoma. The findings were published in two studies in Nature Cancer.
The research, led by Dr. Chan, Daniel McGrail, Ph.D., and Natalie Silver, M.D. M.S., involved analyzing genetic data from patient tumor samples and conducting preclinical model experiments. According to Dr. McGrail’s analysis, it is the overall bacterial load—not specific strains—that appears to weaken the immune response within tumors. Dr. Silver's work confirmed that using antibiotics reduced tumor size and improved immune response, while introducing bacteria made tumors resistant to immunotherapy.
Dr. Silver said, "Immunotherapy is a promising treatment option for patients with head and neck cancer, but the majority unfortunately do not respond. Our research examines how bacteria influence treatment failure. This can help us identify patients most likely to benefit from immunotherapy, with the goal of avoiding unnecessary risk and exposure. Ultimately, we aim to develop targeted interventions that restore the effectiveness of immunotherapy in for patients who do not initially respond."
The team also collaborated with Renata Ferrarotto, M.D., at the University of Texas MD Anderson Cancer Center to examine clinical trial samples from head and neck cancer patients.
In a separate study led by Dr. Chan, researchers analyzed data from the Javelin HN100 Phase III clinical trial which tested whether adding anti-PDL1 immunotherapy to standard chemoradiotherapy would improve outcomes for these patients. The analysis found that those with higher bacterial levels in their tumors had poorer responses to immunotherapy compared to those receiving only chemoradiotherapy. Collaborators included Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute.
Both studies concluded that increased bacteria attract neutrophils—white blood cells responsible for fighting infection—to the tumor microenvironment. While neutrophils are necessary for combating infections, they can suppress immune system activity needed for effective immunotherapy against cancer.
Following these discoveries, Dr. Silver has launched a new clinical trial funded by the American Cancer Society and VeloSano—a Cleveland Clinic fundraising initiative—to test if antibiotics can reduce tumor microbiome levels and enhance patient response to immunotherapy treatments for head and neck squamous cell carcinoma.
Meanwhile, Dr. McGrail continues investigating how bacteria affect cancer development and why some tumors harbor more bacteria than others as part of efforts toward new therapeutic strategies; Dr. Chan is studying whether bacteria might cause DNA mutations within tumors.
"By uncovering the tumor microbiome's role in immunotherapy resistance, these studies mark a significant step forward in understanding the complex interactions between cancer and the immune system," said Dr. McGrail."This research broadens our perspective on cancer treatment and paves the way for developing personalized therapies to improve outcomes for patients."
