Greater Diversity in Gut Microbiome Associated with Better Cancer Immunotherapy Outcomes

Greater Diversity in Gut Microbiome Associated with Better Cancer Immunotherapy Outcomes
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Greater diversity in the gut microbiomes of patients with kidney cancer is linked to better immunotherapy outcomes according to new research from physicians City of Hope and its research affiliate the Translational Genomics Research Institute (TGen). The findings were reported today in the paper “Stool Microbiome Profiling of Patients with Metastatic Renal Cell Carcinoma Receiving Anti–PD-1 Immune Checkpoint Inhibitors” published today in the journal European Urology.

The study, which collected the data from 31 patients with metastatic kidney cancer, marks the first report that compares the sequencing of the gut microbiome at different times in cancer patients.

“We also reported the changes over time in the gut microbiome that occur during the course of therapy — the cumulative findings from our report open the door to therapies directed at the microbiome,” said Sumanta Pal, M.D., one of the study’s senior authors and co-director of the Kidney Cancer Program at City of Hope in a City of Hope press release.

The gut microbiome has received increasing scrutiny in the past few years, as researchers look to chart to its role in a wide range of diseases and health, while also seeking to detail how the microbial populations in patients interact with and affect treatment regimens.

“Previous studies have suggested a relationship between the gut microbiome and response to immunotherapy in solid tumors, including metastatic kidney cancer,” said lead author Nicholas Salgia, a clinical research assistant at City of Hope. “The results from our study build on earlier findings and reaffirm that the diversity and composition of patients’ microbiomes are associated with clinical responses to anti-cancer therapies.”

Using the clinical trial results, the team identified changes in the microbiome over time in kidney cancer patients receiving immunotherapy. The findings showed that the greater the variety of organisms found in a patient’s gut microbiome, the greater the benefit of the therapy to that patient. It also suggested that modulating the gut microbiome during treatment could affect a patient’s responses to therapy.

“The patients with the highest benefit from cancer treatment were those with more microbial diversity, but also those with a higher abundance of a specific bacterium known as Akkermansia muciniphila,” said Sarah Highlander, Ph.D., a research professor in TGen’s Pathogen and Microbiome Division. “This organism has been associated with benefit in other immunotherapy studies.”

Highlander says one potential takeaway is that oncologists might encourage patients to pay attention to their gut microbiome by eating a high-fiber diet, including fruits and vegetables high in fructo-oligosaccharides such as bananas, dried fruit, onions, leeks, garlic, asparagus and artichokes, as well as grains with resistant starches such as barley or uncooked potato starch, for example.

Next steps for the team would be a longitudinal study that expands the relatively small study cohort to a much larger group of patients. Researchers are already further exploring whether modulating the microbiome during therapy could have an impact on clinical outcomes.

“We have randomized patients with metastatic kidney cancer to receive a probiotic supplement in addition to an FDA-approved immunotherapy regimen or the immunotherapy alone,” explained Salgia. “This work provided a strong framework for such a study.”

The collaborations between clinical experts at City of Hope and basic science colleagues at TGen have contributed to advancements in the understanding of not just the microbiome, but also in cancer biology and clinical outcomes at large.

“Our strong relationship with the microbiome team at TGen has fruitfully produced novel insights into the clinical implications of the microbiome in kidney cancer, among other cancer types,” said Pal, who is an internationally recognized leader in the area of genitourinary cancers.