Researchers at the National Cancer Center in Tokyo have identified a specific gut bacteria strain that significantly enhances the effectiveness of cancer immunotherapy drugs in mice, potentially offering a pathway to improve treatment outcomes for the majority of patients who currently don't respond to these therapies.
The study, published in Nature on July 14, reveals that a bacterium called Hominenteromicrobium mulieris, designated as strain YB328, can supercharge the effects of immune checkpoint inhibitors by stimulating dendritic cells in the immune system. These cells then amplify the effects of cancer drugs that unleash the body's own defenses against tumors.
Discovery Through Fecal Transplant Studies
Hiroyoshi Nishikawa, an immunologist at the National Cancer Center in Tokyo, and his colleagues made the discovery while analyzing fecal samples from 50 cancer patients who had been treated with immune checkpoint inhibitors. The team transplanted these samples into mice with tumors and observed that mice receiving transplants from patients who responded well to checkpoint inhibitors benefited more from therapy than those with transplants from non-responders.
"I'm an immunologist, not a microbiologist," Nishikawa said. "I didn't know it would take such a huge effort." The process of identifying the specific microorganism responsible for the enhanced treatment response took his team approximately a year and a half.
Addressing Current Treatment Limitations
Immune checkpoint inhibitors, including drugs like Opdivo and Keytruda, have shown remarkable effects in some patients, sometimes empowering the immune system to drive advanced cancers into long-lasting remission. However, these therapies currently have response rates of only around 20%, meaning they don't work for the majority of people who receive them.
The gut microbiome, comprising over 100 trillion bacteria in the intestines, plays a vital role in human health, affecting the immune system, heart function, and weight. This latest research adds to a growing body of evidence demonstrating the relationship between gut microbes and cancer treatment responses.
Clinical Translation Plans
The discovery of H. mulieris represents what researchers describe as "a really valuable reservoir of bacteria" and a potential "gold mine" for improving cancer treatment outcomes. The research team is now planning clinical trials to test whether this gut microbe can enhance cancer treatment effectiveness in human patients.
The bacterium, discovered only three years ago, thrives in the low-oxygen, nutrient-rich environment of the human intestine. Until this study, H. mulieris had received little scientific attention despite its potential therapeutic significance.
This work represents the latest advancement in increasingly sophisticated studies examining the relationship between the body's microbiome and responses to cancer treatment, offering hope for expanding the reach of immunotherapy drugs to benefit more patients with advanced cancers.
