Immunotherapy, the technique of using the immune system to fight off disease, is one of the most promising avenues for anticancer treatments. However, even with the help of the immune system, not all immunotherapy drugs produce the same response across patients. This variability has been attributed to genetic differences between individuals. And now, a new study reports another cause for drug variability: the bacteria residing in patients’ guts.
In studying the melanoma patients’ variable response to an immunotherapy, researchers at the University of Texas MD Anderson Cancer Center identified a crucial link with the patients’ gut microbiome. Specifically, those with a more diverse microbiome showed better response to the immunotherapy, which led to better outcomes.
The immunotherapy under investigation involves PD-1 immune checkpoint inhibitors. This drug works by blocking a programmed death receptor in the body’s immune cells, allowing these cells to perk up longer and attack the tumor. But while effective, it doesn’t work for everybody. “Anti-PD1 immunotherapy is effective for many, but not all, melanoma patients and responses aren't always durable,” said Jennifer Wargo, an associate professor of Surgical Oncology, and the study’s senior author.
Wargo and her team analyzed the microbiome of 233 melanoma patients through oral swab and fecal samples. They identified a subset of patients who received anti-PD-1 therapy, and classified that group to those who responded and those who didn’t.
This revealed a striking pattern about the microbiome. In particular, Clostridiales bacteria were found in high abundance in the guts of responders. Furthermore, these people had a more diverse range of bacteria. By contrast, those who didn’t respond to immunotherapy had more uniform bacteria species, including a higher concentration of Bacteroidales bacteria.
“Our findings point to two potential impacts from additional research – analyzing the diversity and composition of the microbiome to predict response to immunotherapy and modulating the gut microbiome to enhance treatment,” said Wargo, who is also the co-leader of the Melanoma Moon Shot program.
So far, the results represent the first link between immunotherapy response and microbiome influence. However, to establish causal relationship between these two factors would require careful clinical trials, which Wargo say will begin later this year. Such studies will provide context as to which bacteria are truly beneficial, and how we can modulate these microorganisms to give patients better outcomes.
Additional sources: MD Anderson Cancer Center
