The study suggests that this compound could be combined with common immunotherapies, such as immune checkpoint inhibitors, which stimulate the immune system to target cancer cells.
Dr. Rachel Newsome, a postdoctoral researcher and lead author of the study, said: "Across all cancers, only about 20% of patients respond to immune checkpoint inhibitors, while 80% do not. So any drug that improves the response is very promising."
She added: "We expect the compound to be given in conjunction with or before immunotherapy, increasing patient response by 50% without the need for any additional surgical intervention, and allowing the largest possible number of patients to benefit."
The study was based on years of research into the relationship between gut microbes and the immune system. Dr. Christian Jobin, Distinguished Professor of Medicine and Co-Leader of the Immunology, Oncology, and Microbiome Research Program, explained: "We devised a mechanism to unlock the therapeutic potential of gut microbes through specific steps to reach an active molecule."
In 2018, a collaboration with the Moffitt Cancer Center provided access to stool samples from patients participating in a clinical trial testing immune checkpoint inhibitors. When researchers transplanted stool from patients who had responded to the treatment into mice that had not, they observed an improved response in the mice, confirming the crucial role of gut microbiota in determining the effectiveness of immunotherapy.
The team analyzed the gut microbiota and identified six bacterial strains from among more than 180 that enhanced the mice's response to immunotherapy. However, because fecal cultures or oral administration of bacteria are difficult to implement on a large scale, the researchers focused on the metabolites produced by these bacteria, identifying a single compound called Bac429 that mimics the effects of the six strains.
Newsom said, "When we injected Bac429 into tumors of mice with treatment-resistant lung cancer, tumor growth decreased by 50% after immunotherapy. That's a very big difference."
Researchers are working to develop drug derivatives of Bac429 and understand the precise mechanism by which the molecule interacts with immune cells, which may occur in the gut before they move to attack tumors. While the study focused on lung cancer, researchers anticipate that the molecule will be effective against other types of cancer as well.
The study was published in the journal Cell Reports Medicine.
