Patients with melanoma patients' response to a major form of immunotherapy is associated with the diversity and makeup of trillions of potential allies and enemies found in the digestive tract, according to a study presented at the 1st American Society of Clinical Oncology (ASCO) Clinical Immuno-Oncology Symposium.
An analysis of 113 fecal samples of patients with metastatic melanoma found that those who responded to a PD1 checkpoint inhibitor had a greater diversity of gut bacteria and larger volumes of a specific type of bacteria than those who did not respond.
This connection between a person's microbiome and immune system could have major implications for cancer prognosis and treatment.
"Anti-PD1 immunotherapy is effective for many, but not for all, patients with melanoma and responses aren't always durable," said Jennifer Wargo, MD, University of Texas M. D. Anderson Cancer Center, Houston, Texas.
"Our findings point to 2 potential impacts from additional research: analysing the diversity and composition of the microbiome to predict response to immunotherapy and modulating the gut microbiome to enhance treatment."
The researchers are conducting preclinical research to better understand the mechanisms that connect bacteria and the immune system. They're also designing clinical trials to test the hypothesis that modifying the gut microbiome might improve patients' responses to checkpoint inhibitors.
"Evidence from preclinical research had previously indicated a relationship between solid tumours, immune response, and the microbiome. Our study was the first of its type to look at the relationship between the microbiome and immunotherapy response in patients," said Vancheswaran Gopalakrishnan, University of Texas Health Science Center at Houston School of Public Health, Houston, Texas.
For the current study, the researchers examined oral and gut microbiome samples from 228 patients with metastatic melanoma. While no differences in response were found in connection with the oral samples, the 113 fecal samples told another story. The researchers conducted 16S rRNA sequencing to identify bacteria.
Among the 93 patients treated with anti-PD1 immune checkpoint blockade, the researchers had gut microbiome samples from 30 responders and 13 non-responders. They found that greater diversity of types of bacteria in the responders' microbiomes. They found an increased abundance in responders of the Ruminococcaceae family of bacteria within the Clostridiales order and an increased abundance of Bacteriodales in non-responders and a much lower diversity of bacteria.
The researchers also conducted immune profiling before treatment for the presence of important immune system cells in the tumours. Responders had significantly increased immune infiltrates in their tumours, including the presence of CD8+ killer T cells, correlated to the abundance of a specific bacterium.
"The microbiome is highly targetable in a variety of ways, including by diet, probiotics to boost the presence of helpful bacteria, antibiotics or by fecal transplants," said Dr. Gopalakrishnan.
SOURCE: University of Texas M. D. Anderson Cancer Center
