A new research report, published in the journal Science, is describing how certain species of gut bacteria can enhance the efficacy of cancer immunotherapy. The animal study offers insights into a novel bacteria metabolite-immune pathway that could lead to microbial therapies incorporated into immunotherapy treatments to better treat cancer.
Checkpoint inhibitor immunotherapy has offered doctors a powerful new tool to fight cancer, but the novel treatment does not work in all patients. Several milestone studies over the past few years have investigated what variables could influence the efficacy of cancer immunotherapy, and one particularly influential factor they have homed in on is the gut microbiome.
“Recent studies have provided strong evidence that gut microbiota can positively affect anti-tumour immunity and improve the effectiveness of immunotherapy in treating certain cancers, yet how the bacteria were able to do this remained elusive,” says principle investigator on the new study Kathy McCoy, from the University of Calgary.
The first stage in the new study was to home in on which specific bacteria were influencing the efficacy of cancer immunotherapy. Across four mouse models of cancer, the researchers isolated three particular bacterial species associated with positive immunotherapy outcomes – Bifidobacterium pseudolongum, Lactobacillus johnsonii and Olsenella.
Further investigations revealed inosine, a bacterial metabolite, plays a role in activating anti-tumor T-cells. And this specific mechanism could help explain how gut bacteria can modulate the efficacy of cancer immunotherapy.
“We found that these bacteria produce a small molecule, called inosine,” explains first author Lukas Mager. “Inosine interacts directly with T-cells and together with immunotherapy, it improves the effectiveness of that treatment, in some cases destroying all the colorectal cancer cells.” It is still relatively early days for this research, and many more questions need answers before these findings lead to clinical treatments. For example, inosine breaks down into xanthine and hypoxanthine, so future study must investigate the downstream effects of these metabolites. Plus it is unclear whether inosine by itself could effectively confer the same effect.
The researchers are confident these animal findings will translate to humans, although that will also need to be verified in future studies. The bacterial species focused on in the study have been linked to several cancers in human subjects, so it is hypothetically possible this mechanism applies to humans. The ultimate outcome of the research is hoped to be some kind of adjuvant to immunotherapy to enhance the efficacy of the treatment.
“Identifying how microbes improve immunotherapy is crucial to designing therapies with anti-cancer properties, which may include microbials,” says McCoy. “The microbiome is an amazing collection of billions of bacteria that live within and around us every day.