Doctors have been looking for ways to make immunotherapy more effective for years. This relatively new treatment activates a patient’s own immune system to attack cancer cells. It works remarkably well for some people, but for many others, it does not.
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We now know that there is a link between gut bacteria and the effectiveness of immunotherapy. “Our study helps us understand what gut bacteria do, how they shape our immune system, and how we might use that knowledge to make immunotherapy more effective,” says researcher Iris Mimpen, from the Emile Voest lab at the Netherlands Cancer Institute and Oncode Institute.
Most of the microbes living in and on us, reside in our intestines. They help digest our food and produce vitamins. But which of these millions of bacteria interact with immunotherapy? If we can uncover that, we might be able to support or even supply the most helpful ones.
The challenge is that everyone’s gut bacteria are different. As a result, past studies pointed to a wide variety of bacterial species that appear to be linked to immunotherapy. These findings are difficult to translate into patient care.
So the Voest lab took a different approach. Instead of looking at which bacteria are present, they asked themselves what kinds of signaling molecules the microbes collectively produced. “It’s like politics,” explains Iris. “If you want to understand Brussels, it’s not enough to just know the names of the politicians. You need to know what they say and do.”
The team analyzed stool samples from nearly 800 patients who had previously received immunotherapy. They also collected fresh samples and tumor data from 147 new patients and studied how bacterial signaling molecules could affect the immune cells.
“Focusing on the things these bacteria can do led to interesting findings,” says Iris. “We identified several bacterial molecules that can stimulate helpful immune cells, such as HMBPP. Patients whose gut bacteria produced more of this molecule responded better to immunotherapy. On the other hand, we also found molecules that suppress the immune system, which were more common in patients who responded poorly.”
The good news is that these molecules appeared consistently across all patient groups from earlier studies. “The specific bacterial species vary greatly between individuals, making that links between a specific type of bacteria and the effects of the therapy can be coincidental”, says Iris. “But these molecules do show up consistently. That means that this bacterial behavior, their collective ‘output,’ may be a much more reliable predictor of whether immunotherapy will work. We now want to explore whether patients will respond better to immunotherapy if we provide certain molecules or bacteria.”
Unfortunately, the research team had to continue their work without researcher Tom Battaglia. “He passed away from cancer earlier this year, which greatly affected us all,” Iris shares. “It’s strange to present these findings without him, because this work would not have been possible without him. His passing reminds me of why I do this work, as did climbing the Italian mountains this summer to raise funds for cancer research through Stelvio for Life.”
The microbiome, the community of all microorganisms living in and on our bodies, is drawing more and more attention from cancer researchers. They wonder whether bacteria can affect how cancer cells behave. Or how chemotherapy works. Just last year, Voest’s group discovered that certain bacteria can even be found inside cancer metastases.
This research was financially made possible by the AVL Foundation, KWF Dutch Cancer Society, and Oncode Institute.