Bacteria Found in Lung Tumors May Boost Immune Response to Cancer
08/19/2026
Bacteria in lung tumors may boost the activation of innate immune cells in the presence of a common vitamin metabolite, according to a preclinical study by researchers from the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy.
The study was published Aug. 18 in the Proceedings of the National Academy of Sciences.
It suggests a new way to stimulate the immune system to attack cancer. The study showed that adding a metabolite of vitamin B2 to bacteria found in lung tumors led to the increase in cell surface expression of a protein called MR1 on antigen-presenting immune cells, which activates innate immune cells called mucosal-associated invariant T-cells (MAIT).
“We are opening a new field of immunotherapy by using a metabolite that, in combination with these bacteria, increases the expression of MR1 and triggers the activation of MAIT cells toward the tumor,” says Franck Housseau, Ph.D., PharmD, an associate professor of oncology at the Johns Hopkins University School of Medicine, now research director of the French National Institute of Health and Medical Research, who studies interactions between the microbiome and tumors in the response to immunotherapy.
Many emerging cancer therapies, such as immune checkpoint inhibitors, focus on reinvigorating the adaptive immune system’s T cells to help them recognize and destroy tumor cells. Less attention has been paid to MAIT cells, Housseau says. MAIT cells act as first responders to injury or infection, detecting and destroying threats at the mucosa that forms a barrier to the outside world. But there is emerging research on how these cells might also be used to fight cancers.
MAIT cells recognize a protein called MR1 that antigen-presenting immune cells express in response to bacteria, injury or other dangers. But microbiome sequencing of human tumors and RNA sequencing of immune cells from patient samples, along with cell culture experiments, revealed an unexpected finding. Housseau and his team expected bacteria that produce the B2 metabolite to activate MAIT cells, but one of the non-B2-metabolite-producing enterococci bacteria also greatly enhanced MAIT cell activation when a B2 metabolite was added to cell cultures.
“Tumor-associated bacteria may regulate the immune response to tumors by regulating the expression of MR1 on antigen-presenting cells and activating the MAIT cells in the tumor microenvironment, which could have anti-tumor effects,” explains Pakhi Birla, Ph.D., a cancer immunologist who led the study while completing her doctorate in the laboratories of Housseau and Drew Pardoll, M.D., Ph.D.
From a previously published study by Pardoll and Kellie Smith, Ph.D., an associate professor of oncology at Johns Hopkins Medicine, of lung cancer patients treated with neoadjuvant PD-1 blockade immunotherapy, Birla found that a patient who had a strong response to therapy had many MAIT cells, suggesting it may have contributed to the patient’s therapeutic success.
This novel discovery was facilitated by an interdisciplinary collaboration between Housseau, an expert in mucosal immunology; Pardoll, director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy and an expert in tumor immunology and immunotherapy; Cynthia L. Sears, M.D., an infectious diseases expert and the Bloomberg~Kimmel Professor of Cancer Immunotherapy at Johns Hopkins; and Fyza Y. Shaikh, M.D., Ph.D., an assistant professor of cancer immunology at Johns Hopkins Medicine.
The team has already begun preclinical studies to determine whether injecting the B2 metabolite into the lung tumors of mice may stimulate an immune response. They also plan to study whether they can engineer adaptive immune T cells to recognize MR1 to help them target tumor cells. Unlike existing adaptive immune T cell therapies, which are customized to target proteins specific to an individual patient, T cell therapies targeting MR1 could work for almost any patient.
“It is very expensive and very complex to personalize immunotherapy, maybe not accessible to every patient,” Housseau explains. “But if we are successful, we could develop a new concept: tumor-agnostic, off-the-shelf therapy that works for every patient.”
Study co-authors were Lanasol Yang, Wanting Shan, Omkar Dhaygude, Haritha Manoj, Alex Lee, Jacqueline Ferri, Ying Zheng, Andrew Northcutt, Hongni Fan, Hadley Beauregard, Zhen Zeng, Fyza Shaikh, Smith and Pardoll of Johns Hopkins; and Sakura Minamisawa of Juntendo University in Tokyo.
The research was supported by the Commonwealth Foundation and the Bloomberg~Kimmel Institute for Cancer Immunotherapy.
The researchers reported no competing interests.
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