A study links some qualities of patients’ microbiomes to rapid progression of metastatic melanoma—while other qualities

The more diverse the digestive tract bacteria, the slower the progression of metastatic melanoma in patients treated with immunotherapy, researchers at The University of Texas MD Anderson Cancer Center reported today.

At the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, the researchers presented results from a study of fecal samples from 105 patients treated with immune checkpoint blockade.

Those results linked some qualities of patients’ microbiomes to rapid progression of metastatic melanoma—while other qualities, such as an abundance of specific bacteria, correlated with both a higher response rate to treatment and longer progression-free survival (PFS).

In the study, researchers found that patients with more varied types of bacteria in their digestive tract had longer median PFS. As a median time to follow-up of 242 days, the patient group with high microbiome diversity had not reached median PFS, while those with intermediate diversity had median PFS of 232 days and those with lower diversity had median PFS of 188 days, MD Anderson said.

More than half of those with abundant F.prausnitzii had not reached median PFS, while half of those with low abundance had their disease progress by 242 days.

An abundance of Bacteroidales was associated with more rapid disease progression. Patients with abundant levels of the bacterium showed a median PFS of 188 days, compared to a median PFS of 393 days for those with lower levels.

Researchers determined microbiome composition from fecal samples by conducting an analysis of the presence of 16S ribosomal RNA used to identify bacteria. Whole genome sequencing and immune monitoring were conducted on the tumors after treatment and in some tumors before treatment. Immune profiling showed that responders to anti-PD1 treatment had significantly increased immune infiltrates in their tumors, including the presence of CD8+ killer T cells, correlated to the abundance of a specific bacterium.

“The microbiome appears to shape a patient’s response to cancer immunotherapy, which opens potential pathways to use it to assess a patient’s fitness for immunotherapy and to manipulate it to improve treatment,” Jennifer Wargo, M.D., associate professor of surgical oncology at MD Anderson and leader of the study, said in a statement.

Dr. Wargo is also co-leader of the Melanoma Moon Shot™, part of MD Anderson’s Moon Shots Program™. Announced in 2012, the “Moon Shots” program consists of partnerships designed to speed up translation of scientific discoveries into clinical advances that significantly reduce cancer deaths.

In addition to melanoma, MD Anderson’s “Moon Shots” cancer areas of focus include B-cell lymphoma, breast, colorectal, lung, glioblastoma (brain cancer), cancers caused by the human papillomavirus, chronic lymphocytic leukemia, myelodysplastic syndrome and acute myeloid leukemia, multiple myeloma, ovarian, pancreatic, and prostate.

Dr. Wargo’s team is working with researchers at the Parker Institute for Cancer Immunotherapy (PICI) to develop the first immunotherapy-microbiome clinical trial, which they hope to launch later this year.

As those trials develop, Dr. Wargo and colleagues also are carrying out lab and mouse model research into the mechanisms that connect bacteria and the immune system.

That work, MD Anderson said, will include a project designed to provide favorable and unfavorable microbiomes to study through fecal transplants from patients who responded to therapy, as well as from non-responders, into germ-free mice. The project will be funded by Stand Up to Cancer, the charitable effort that promotes accelerated translational cancer research.

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