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Diverse gut microbiome may improve response to immunotherapy for melanoma
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Patients with melanoma who responded to immunotherapy had a more diverse gut microbiome than nonresponders, according to study results scheduled for presentation at the 2017 ASCO-SITC Clinical Immuno-Oncology Symposium.
These results suggest that modifications to the gut microbiome could potentially improve a patient’s response to anti–PD-1 therapy.
There are 100 trillion bacteria — including more than 1,000 different species — in the gut, and the composition of the microbiome can be different for each individual.
Animal studies have suggested that modulation of the gut microbiome could enhance responses to immune checkpoint blockades in melanoma.
“There has been growing appreciation for the important role that the microbiome plays in immune defenses against cancer, with much of the work being done in mouse models,” Jennifer A. Wargo, MD, MMSc, associate professor of genomic medicine and surgical oncology at the University of Texas MD Anderson Cancer Center, said in a press release. “To our knowledge, this is one of the first studies to explore the association between the microbiome and immunotherapy response in people.”
Therefore, Wargo and colleagues collected oral and gut microbiome samples from 233 patients with advanced melanoma who were initiating therapy. Ninety-three patients were treated with anti–PD-1 therapy.
Patients who responded to PD-1 inhibitors showed significant differences in the diversity and composition of gut microbiomes at baseline compared with nonresponders; however, no difference in oral microbiomes were observed.
For instance, patients who responded to treatment showed an increased amount of Clostridiales bacterium — specifically the Ruminococcaceae family — in the gut microbiome, whereas patients who did not respond showed a greater abundance of Bacteroidales bacterium.
Responders also showed a significantly higher alpha diversity compared with nonresponders (P = .017).
Immune profiling demonstrated significantly increased immune infiltrates in baseline tumor samples of patients who responded to treatment — including a positive correlation between CD8, CD3, PD-1 and FoxP3 T-cell density — compared with those who did not respond to immune checkpoint inhibitors. Further, CD8–positive T cells in the tumor appeared associated with a higher abundance of specific types of bacteria of the Ruminococcaceae family in the gut microbiome.
Oral microbiome samples showed no association between diversity or composition and response to therapy.
“Our findings are early, but if they are validated in larger cohorts across cancer types, they may have significant implications for cancer prognosis and treatment,” Wargo said. “Meanwhile, we need concerted research efforts to better understand how the microbiome may influence immune responses, as well as an in-depth view on how we can tweak the microbiome so that more patients can benefit from immunotherapy.”
Other strategies may involve the use of antibiotics to selectively deplete certain bacteria or the use of pre- or probiotic supplements to enhance certain bacteria into the gut, according to the researchers.
“Immunotherapy is rapidly improving the lives of people with cancer, but it doesn’t work for many patients, and we still don’t know why,” Lynn Schuchter, MD, FASCO, chief of the division of hematology and oncology at the Perelman Center for Advanced Medicine, attending physician at Hospital of the University of Pennsylvania, and an ASCO expert who was not involved in the study, said in the release. “These results open the door for new approaches to boosting patients’ responses to PD-1 drugs, potentially by tinkering with the composition of gut bacteria.” – by Kristie L. Kahl
Reference:
Vancheswaran G, et al. Abstract 2. Presented at: ASCO-SITC Clinical Immuno-Oncology Symposium; Feb. 24-26; Orlando, Fla.
Disclosure: This study was supported by the Moon Shots Program at The University of Texas MD Anderson Cancer Center, the Melanoma Research Alliance and the Parker Institute for Cancer Immunotherapy. Please see the abstract for a list of all the researchers’ relevant financial disclosures.