How the Gut Microbiome Is Affecting Immunotherapy Response

Bacteria in the gut microbiome may be regulating how a tumor responds to checkpoint blockade immunotherapy, according to a study of pre-clinical mouse models. The research was published in the journal Science.

The authors examined the oral and gut microbiome of patients with metastatic melanoma who were being treated with anti—PD-1 immunotherapy. They determined that the patients with a more diverse population of gut bacteria or an abundance of certain types of bacteria were more likely to have their disease controlled for longer.

“You can change your microbiome, it’s really not that difficult, so we think these findings open up huge new opportunities,” study leader Jennifer Wargo, MD, associate professor of surgical oncology and genomic medicine at MD Anderson Cancer Center, said in a statement. “Our studies in patients and subsequent mouse research really drive home that our gut microbiomes modulate both systemic and anti-tumor immunity.”

Diet, exercise, antibiotic or probiotic use, or transplantation of fecal material can all potentially be used to target and modify a person’s microbiome. With only 25% of patients with metastatic melanoma benefitting from immunotherapy drugs and the responses not always durable, researchers are trying to find ways to extend the impact of immune checkpoint blockade drugs.

The researchers analyzed tissue samples from inside the cheek and fecal samples of patients who received a PD-1 inhibitor, then conducted 16S rRNA and whole genome sequencing to determine the diversity, composition, and functional potential of the microbiomes. The cheek samples did not yield any substantial differences in response or progression, but fecal samples did.

Patients with a higher diversity of bacteria in their gut had a longer median progression-free survival (PFS). Those with high diversity hadn’t reached median PFS, but those with intermediate diversity had PFS of 232 days and those with low diversity had PFS of 188 days. Patients with a high abundance of the bacteria Faecalibacterium had not reached median PFS, while patients with a low abundance of the bacteria had a median PFS of 242 days.

The authors are working to develop a clinical trial that combines immune checkpoint inhibitor treatment with microbiome modulation.

“Immune profiling suggested enhanced systemic and anti-tumor immunity in responding patients with a favorable gut microbiome, as well as in germ-free mice receiving fecal transplants from responding patients,” the authors concluded. “Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors."