What is already known on this topic
Less than 50% of people with melanoma respond to cancer immunotherapy. While several studies have linked the composition of the gut microbiota with a person’s response to immunotherapy, little is known about the specific microbiota characteristics the can lead to clinical benefits.
What this research adds
Researchers collected stool samples from 175 people with advanced melanoma who received immune checkpoint inhibitor treatment, a type of immunotherapy. They found that three types of bacteria — Akkermansia muciniphila, Bifidobacterium pseudocatenulatum and Roseburia species — were associated with a better response to immunotherapy, but no single species could be used as a reproducible biomarker across different groups of patients. That’s likely because several factors, including a person’s diet and the use of specific drugs before immunotherapy, influence the microbiota composition, the researchers found.
Conclusions
The findings suggest that studying gut microbes can help to improve and personalize immunotherapy treatments for melanoma. However, future studies should take into account the influence of diet and other factors on the composition of the gut microbiota during immunotherapy.
Melanoma is the most dangerous type of skin cancer and one of the most common cancers in people under 30. Now, researchers have confirmed the link between gut microbes and the response to a specific treatment for melanoma.
The findings, published in Nature Medicine, could help to develop microbiota-based strategies to advance immunotherapy treatments for melanoma. “Our study shows that studying the microbiome is important to improve and personalize immunotherapy treatments for melanoma,” says study senior author Nicola Segata at the University of Trento. “However, it also suggests that because of the person-to-person variability of the gut microbiome, even larger studies must be carried out to understand the specific gut microbial features that are more likely to lead to a positive response to immunotherapy.”
Less than 50% of people with melanoma respond to cancer immunotherapy. While several studies have linked the composition of the gut microbiota with a person’s response to immunotherapy, little is known about the specific microbiota characteristics the can lead to clinical benefits.
To fill this knowledge gap, Segata and his colleagues analyzed the microbiota of people with advanced melanoma who received immune checkpoint inhibitor treatment, a type of immunotherapy.
Better response
The researchers collected stool samples from 175 melanoma patients across five clinical centers in the United Kingdom, the Netherlands and Spain. Then, they sequenced the microbial DNA present in the samples to uncover potential associations between the composition of the gut microbiota and a patient’s response to immunotherapy.
The team confirmed previous results that showed that the gut microbiota is associated with response to immune checkpoint inhibitor treatment. The researchers found that people with high abundances of three types of bacteria — Akkermansia muciniphila, Bifidobacterium pseudocatenulatum and Roseburia species — were more likely to respond to immunotherapy better than those with lower levels of the bacteria.
“This study shows the chances of survival based on healthy microbes nearly doubled between subgroups,” says study senior author Tim Spector at King’s College London.
Confounding factors
Although the presence of specific bacteria appears to be associated with a better response to immunotherapy, no single species could be used as a reproducible biomarker across different groups of patients. The researchers speculated that this limited reproducibility could be due to clinical factors that affect the microbiota, thus confounding the association between a person’s microbiota composition and their response to immunotherapy.
Indeed, the team’s analysis revealed that factors including diet and the use of specific drugs before immunotherapy can influence the microbiota. However, these associations between clinical factors and gut microbes appeared to be independent of a patient’s response to immune checkpoint inhibitor treatment.
The researchers note that future studies should take into account the influence of diet and other factors on the composition of the gut microbiota during immunotherapy. “The ultimate goal is to identify which specific features of the microbiome are directly influencing the clinical benefits of immunotherapy to exploit these features in new personalized approaches to support cancer immunotherapy,” Spector says.
