The bacterial community that lives in our guts, aiding in digestion and also impacting our health, has now been shown to influence the growth of pancreatic cancer. Researchers assessed pancreatic tumor samples and found that they contained a high level of bacteria compared to healthy pancreatic tissue, and that gut bacteria migrate there when cancer occurs. They followed up with a mouse model and found that when certain types of bacteria were eliminated, the growth of pancreatic cancer slowed.
"The gut microbiome has been studied in many different cancers, including liver and colorectal cancer, and is shown to affect cancer progression," said George Miller, MD, the HL Pachter Professor in the Departments of Surgery and Cell Biology at New York University School of Medicine. "Because the pancreas is remote from the gut, it is considered a sterile organ, and there haven't been many studies that looked at the role of the gut microbiome in pancreatic cancer."
By comparing fecal samples from 32 people with pancreatic ductal adenocarcinoma to that of healthy people, the bacterial composition in the patients was found to be very different. "The bacterial composition was more diverse in the fecal samples than from cancer patients," revealed Miller.
"The dysbiosis in the gut microbiome can potentially be used as a biomarker to define a high-risk population," added Deepak Saxena, Ph.D., associate professor in the Department of Basic Science and Craniofacial Biology at New York University College of Dentistry. Some of the more prevalent strains of bacteria that were identified in pancreatic cancer patients were Bacteroidetes, Firmicutes, and Proteobacteria.
The investigators observed that in their mouse model of pancreatic cancer, bacteria moved from the gut to the pancreas. Further research showed that when antimicrobial treatment was used to remove those bacteria, the growth of the cancer was slowed, reducing the tumor burden by around 50 percent. This process also increased the infiltration of T-cells into the tumor, as well as in increase in the expression of PD1 on T-cells inside the tumors.
"We were surprised to see that the human pancreatic tissue samples had an active microbiome," said Saxena. "And we found that not only are there bacteria in the pancreas but the bacterial load is significantly higher in pancreatic cancer tissue compared to normal pancreas tissue."
When bacteria were reintroduced to the treated mice, the tumor protection was reversed. Taken together, this work suggests that the microbiome can influence pancreatic ductal adenocarcinoma by affecting the tumor’s immune suppression. When the scientists combined anti-PD1 immunotherapy with immune suppression, T-cell activation was enhanced.
"Our studies show that the bacteria may serve both as biomarkers of increased risk for pancreatic cancer as well as potential therapeutic targets," said Miller. "We believe that targeting the microbiome in patients with pancreatic cancer can make immunotherapy effective."
"Pancreatic cancer is a very aggressive disease with a five-year survival rate of a dismal 8.2 percent,” noted Saxena. “Extending the life of these patients by manipulating the microbiome and decelerating tumor progression would be a significant step forward in managing this deadly disease."
The researchers have planned a clinical trial in patients with pancreatic ductal cancer to test treatment with an antibody against PD1 and two antibiotics, ciprofloxacin and metronidazole.
Learn more about how the microbiome influences immunotherapy from the video.