Bacteria in our gut might help decide whether cancer immunotherapy works. But until now, it wasn’t clear which bacteria matter - or how. Researchers from the lab of Oncode Investigator Emile Voest (the Netherlands Cancer Institute) have found new leads by looking not at who is there, but what they do.
Understanding immunotherapy
The study, published now in Cancer Discovery, points to molecules produced by gut microbes that could influence treatment outcomes. Immunotherapy is a treatment that activates a patient’s own immune system to attack cancer cells. For some, it works wonders. For others, the response is weak. Scientists have long suspected that gut bacteria play a role.
“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 Oncode Researcher Iris Mimpen.
Not just names, but actions
The gut is full of microbes that help digest food and produce vitamins. But which ones actually affect immunotherapy? Past studies focused on bacterial species, which vary widely between people. That made it hard to draw clear conclusions.
The Voest group decided to focus on the molecules bacteria produce — the signals they send to immune cells.
“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.”
Molecules that matter
The team analyzed stool samples from nearly 800 patients who had received immunotherapy, plus fresh samples from 147 more patients. They looked at how bacterial molecules influenced 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, molecules that suppress the immune system were more common in patients who responded poorly.”
Unlike bacterial species, which differ between individuals, these molecules appeared consistently across all patient groups. “That means the bacteria’s collective ‘output’ may be a much more reliable predictor of whether immunotherapy will work,” Iris adds. “We now want to explore whether patients will respond better to immunotherapy if we provide certain molecules or bacteria.”
A personal note
The study was carried out under difficult circumstances. Oncode Researcher Tom Battaglia, a driving force behind the work, passed away from cancer earlier this year.
“It’s strange to present these findings without him, because this work would not have been possible without him,” says Iris. “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.”
Impact on science and health
This research provides a fresh perspective on gut bacteria and immunotherapy. By looking at bacterial behavior instead of species, the study identifies reliable molecular predictors of treatment response.
These insights could help doctors predict which patients are most likely to benefit from immunotherapy and design interventions to enhance treatment, for example by supplying specific molecules or supporting beneficial bacteria. It could also help understand why immunotherapy fails in some patients and improve outcomes.
The study also highlights the broader role of the microbiome in cancer care. Previous work shows bacteria can influence tumor growth, chemotherapy response, and even colonize metastases.
This work was made possible thanks to support from the AVL Foundation, KWF Dutch Cancer Society, and Oncode Institute.