Discovery of gut microbiota that enhance the effectiveness of "cancer immunotherapy" — National Cancer Center Japan and others

A joint research group from the National Cancer Center Japan and other institutions announced the discovery of new gut microbiota that enhance the treatment effectiveness of "cancer immunotherapy," which strengthens the immune system's ability to attack cancer cells. About 20% of Japanese people are believed to carry these bacteria. The research group aims to develop therapies that will be effective for more patients, including those who previously showed low response to this treatment.

Cancer immunotherapy drugs are called "immune checkpoint inhibitors," and release the "brakes" that cancer cells use to suppress immune cell function and strengthen their attack power against cancer cells. Research by Dr. Tasuku Honjo, who won the Nobel Prize in Physiology or Medicine, led to the development of these drugs. Several drugs, including "Opdivo," are known. This is called the "fourth cancer treatment" following surgery, radiation therapy, and chemotherapy, and expectations are high.

However, according to the National Cancer Center Research Institute, even when immune checkpoint inhibitors are used in combination with other drugs, they are not sufficiently effective on more than half of patients, and only about 20% of patients show long-term treatment effects. While the possibility that gut microbiota are involved in treatment effectiveness had been pointed out, the details were unclear.

A research team led by Chief Hiroyoshi Nishikawa of the Division of Cancer Immunology at the National Cancer Center Research Institute, analyzed the relationship between cancer immunotherapy effectiveness and gut microbiota in 50 patients with gastric cancer and non-small cell lung cancer who underwent cancer immunotherapy.

As a result, they found that the stool of patients who responded well to the drug contained significantly more bacteria from the "Ruminococcaceae" family compared with patients who did not experience sufficient effects. This was a previously unknown bacterium, which the researchers isolated, cultured, and analyzed in detail, naming it "YB328."

To investigate the function and properties of this gut microbiota YB328, experiments were conducted by administering it to mice, resulting in tumor shrinkage in the mice. Further investigation revealed that it activates "dendritic cells," which are considered the command center of the immune system.

Dendritic cells play an important role by taking up foreign substances such as cancer cells, presenting antigens, and issuing commands to "attack these foreign substances." In mice that received oral administration of YB328, the bacterium had migrated to sites where cancer was present. The research group has suggested that dendritic cells activated by YB328 migrate to cancer tissues and enhance the action of other immune cells called "T cells."

Furthermore, when examining cancer tissues collected from patients, they confirmed that patients with high YB328 possession rates had many activated dendritic cells and T cells infiltrating their cancer tissues. According to the National Cancer Center Research Institute, preparations for clinical applications are already underway with a startup company originating from the Center.

It is becoming clear that gut microbiota are involved in various diseases, immune mechanisms, aging, and other processes. In May, the Center published research findings showing that 50% of Japanese colorectal cancer patients had genomic changes caused by toxins secreted by certain gut microbiota, continuing their investigation into the relationship between cancer and gut microbiota.

The joint research group that announced these findings received support from Goal 7 of the national large-scale research program "Moonshot" and others, with Nishikawa's team at the National Cancer Center Research Institute as the core, along with research members from the National Institute of Advanced Industrial Science and Technology, RIKEN, and universities in Nagoya, Kyoto, and Osaka. The research results were published in the British scientific journal Nature on July 14.