Gut microbiome a player in response to anti-PD-1 cancer immunotherapy

Last Updated: 2017-02-22

By Reuters Staff

NEW YORK (Reuters Health) - The gut microbiome may play a role in response to anti-PD-1 immune checkpoint inhibitor therapy, new research suggests.

The study in patients with metastatic melanoma found that a patient's ability to respond to the treatment hinged on the presence of a diverse microbiome as well as specific bacterial species.

The findings were released February 21 ahead of a presentation later this week at the inaugural American Society of Clinical Oncology (ASCO)/Society for Immunotherapy of Cancer (SITC) Clinical Immuno-Oncology Symposium in Orlando, Florida.

“There has been a 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. To our knowledge, this is one of the first studies to explore the association between the microbiome and immunotherapy response in people,” lead investigator Vancheswaran Gopalakrishnan, a PhD candidate at the University of Texas School Of Public Health in Houston, said in a conference statement.

The researchers analyzed fecal microbiome samples from 233 patients with metastatic melanoma initiating therapy, including 93 who started an anti-PD-1 inhibitor. Patients were classified as either responder or non-responder to anti-PD-1 therapy based on RECIST criteria.

The researchers used 16S rRNA gene sequencing to assess the diversity and composition of the oral and gut microbiome. They also analyzed the composition and density of various immune cells in patient tumor samples.

There were significant differences in the gut microbiome of responders and non-responders to PD-1 inhibitors, according to the researchers.

Anti-PD-1 responders showed a more diverse gut microbiome than non-responders, although the sample size was somewhat limited (30 responders and 12 non-responders), they note.

There were also “notable differences” in the composition of the gut microbiome in responders versus non-responders. Patients who responded to treatment had an increased abundance of Clostridiales bacteria (specifically the Ruminococcaceae family) in the gut microbiome relative to non-responders. Patients who did not respond showed a greater abundance of Bacteroidales bacteria relative to responders.

In addition, patients who responded to PD-1 inhibitor therapy also had a higher density of cytotoxic CD8+ T cells in the tumor microenvironment than non-responders. There was also an association between CD8+ T cells in the tumor and a higher abundance of specific types of commensal bacteria of the Ruminococcaceae family in the gut microbiome.

“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,” Dr. Jennifer A. Wargo, the study's senior author, said in the statement.

“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,” added Dr. Wargo of the University of Texas MD Anderson Cancer Center in Houston.

The researchers are now designing clinical trials to test the hypothesis that modulation of the gut microbiome may enhance responses to immune checkpoint inhibitors. The first such trial is expected to get underway later this year.

In a conference statement, ASCO expert Dr. Lynn Schuchter from University of Pennsylvania said, "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. 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.”

The study was supported by the Moon Shot program at MD Anderson Cancer Center, the Melanoma Research Alliance and the Parker Institute for Cancer Immunotherapy. Several authors disclosed financial relationships with various pharmaceutical companies.

SOURCE: http://bit.ly/2l5mzmd

2017 ASCO-SITC Clinical Immuno-Oncology Symposium.