Japan research team discovers new gut bacterium that boosts cancer immunotherapy
Cancer immunotherapy leverages the body's immune system to attack cancer cells. One class of drugs, known as immune checkpoint inhibitors -- including PD-1 inhibitors such as Opdivo -- works by releasing the "brakes" that cancer uses to evade immune cell attacks, thereby restoring the immune system's natural ability to target tumors.
However, even when used in combination with other treatments, checkpoint inhibitors are effective in only about 20% of patients over the long term. Previous studies have shown that transplanting stool from patients who responded well to these drugs into non-responders can improve outcomes, suggesting that gut bacteria play a key role. Until now, the mechanism by which gut bacteria influence cancers located far from the intestines, such as in the lungs, was not well understood.
The research team found that patients who responded well to immunotherapy had high levels of a type of gut bacterium from the Ruminococcaceae family. These patients experienced longer-lasting treatment effects and had more T cells -- immune cells that attack cancer -- present within their tumors.
The team identified this bacterium as a new strain, named YB328. In mouse experiments, administering both checkpoint inhibitors and YB328 led to tumor shrinkage, and even when YB328 was given together with stool transplanted from non-responders, the drug's effectiveness improved.
Further investigation revealed that YB328 activates dendritic cells -- immune system "commanders" that orchestrate immune responses -- in the gut. These dendritic cells then travel from the intestines to distant tumor sites, where they activate nearby T cells and enhance the immune attack on cancer.
Hiroyoshi Nishikawa, head of the Cancer Immunology division at the National Cancer Center Research Institute, commented, "Not only could administering this bacterium to (drug) non-responders improve outcomes, but adding it to responders' treatment regimens may further boost effectiveness."
https://doi.org/10.1038/s41586-025-09249-8
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