Bacteria On Tumors Influences Immune Response, Survival Of Patients With Pancreatic Cancer

By Bio-IT World Staff

August 9, 2019 | A team led by researchers from The University of Texas MD Anderson Cancer Center reports that a key difference between the few pancreatic cancer patients who survive long-term and the many whose disease overcomes all treatments is the bacterial signatures on their tumors that either stimulate or suppress immune response. The team's findings were published in the journal Cell (DOI: https://doi.org/10.1016/j.cell.2019.07.008).

The researchers also showed that fecal microbiota transplants (FMT) from long-term survivors prompted immune response and stifled tumors in a mouse model of the disease by altering the bacteria on the tumor—its microbiome.

"Results of the FMT experiments represent a significant therapeutic opportunity to improve pancreatic cancer treatment by altering the tumor immune microenvironment," senior author Florencia McAllister, assistant professor of Clinical Cancer Prevention at MD Anderson, said in an official statement. "There is promise here but we have a lot of work ahead."

MD Anderson's Pancreatic Cancer Moon Shot has provided McAllister with funding to develop a clinical trial of fecal transplants for pancreatic cancer. The Moon Shots Program is a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients' lives.

Most patients with pancreatic ductal adenocarcinoma—the most common form of pancreatic cancer—have late-stage disease when diagnosed. Just 9% survive to five years. Those with earlier stage cancer that can be surgically removed have a high recurrence rate and median survival of 24-30 months.

No genomic biomarkers have been identified that shed light on the reasons for long-term survival in that fraction of patients, McAllister said.

Long-term survivors have diverse tumor microbiome

While recent research has shown that the composition and diversity of microbes living in the digestive tract—the gut microbiome—can affect how cancer immunotherapy works, little research has focused on the bacteria in the tumor and how it might affect prognosis and survival, McAllister said. "We've known there are bacteria on pancreatic tumors, so we asked 'do these bacteria have a role in cancer?'"

To launch the first such study in pancreatic cancer, McAllister and colleagues analyzed the bacterial DNA in tumors of long-term survivors matched to short-term survivors from two independent cohorts at MD Anderson and Johns Hopkins Hospital. In the MD Anderson cohort, median survival was 10 years for the long-term survivors (22 patients) and 1.6 years for the short-term survivors (21 patients). In the validation cohort from Johns Hopkins, 15 patients had overall survival greater than 10 years, and 10 survived fewer than five years.

Using 16S rRNA gene sequencing, the team found the long-term survivors had much greater diversity of bacterial species than the short-term survivors. Stratifying the MD Anderson patients only by this diversity measure showed those with high diversity had median survival of 9.66 years and those with low diversity had median survival of 1.66 years.

The diversity results were independent of other factors, such as previous therapies, body mass index, and antibiotics use, making it a predictor of survival for surgical patients and indicating the potential importance of the tumor microbiome in cancer progression.

Researchers also found marked differences in the bacterial communities found in each survivor group. The long-term survivors showed a relative abundance of Pseudoxanthomonas, Saccharropolyspora and Streptomyces. The presence of all three taxa, as well as the species Bacillus Clausii, predicted better outcomes for patients in both MD Anderson and Johns Hopkins cohorts.