ImmunologyMicrobiology

Bacteria May Stimulate Pancreatic Cancer by Inhibiting Immune System

In a new study, scientists discovered that bacteria suppress the immune system which in turn promotes pancreatic cancer. The research proposes that targeting the microbiome may make immunotherapy effective against pancreatic cancer.

In many types of cancer like liver and colorectal cancer, gut microbiome is studied and it has been observed that it affects the development of cancer. The gut microbiome is the microbes population living in our intestine. As the pancreas is isolated from the gut, there haven’t been many studies that looked at the role of the gut microbiome in pancreatic cancer because the pancreas is considered as a sterile organ.

During their research, researchers took fecal samples from 32 patients suffering from pancreatic ductal adenocarcinoma and compared them with samples from normal individuals and found out that Bacterial load was significantly higher in patients suffering from a pancreatic tumor. According to the author, the bacterial composition was more diverse in the fecal samples than from cancer patients.

Author Deepak Saxena Ph.D., associate professor in the Department of Basic Science and Craniofacial Biology at New York University College of Dentistry says “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.”

After that researchers conducted their study in the mouse by translocating the bacteria from the gut to pancreas. They observed that by eliminating these bacteria using antimicrobial treatment, the progression of pancreatic cancer slows down the tumor burden was also decreases by 50 percent. This process also affected T-cell differentiation, leading to increased T-cell infiltration into the tumor and reduction in myeloid-derived suppressor cell (MDSC) population. Antimicrobial treatment also resulted in increased expression of PD1 on CD4+ and CD8+ T cells within the tumors.

Researchers found the Proteobacteria, Bacteroidetes, and Firmicutes bacterial strains most abundant in the pancreatic cancer patients and concluded that to define the high-risk population of bad bacteria,  dysbiosis (imbalance) in the gut microbiome can potentially be used as a biomarker.

“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.”

In their further studies, researchers reintroduced bacteria in antimicrobial treated mice and showed that it reduces the immunogenicity of the tumors and reverse the tumor protection, suggesting that the microbiome promotes pancreatic ductal adenocarcinoma by inducing immune suppression in the tumor.

The researchers also found that combining antimicrobial treatment with an anti-PD1 immunotherapy resulted in enhanced CD4+ and CD8+ T-cell activation in mice, suggesting that such a combination is a potential treatment option for pancreatic ductal adenocarcinoma.

The author added that “Pancreatic cancer is a very aggressive disease with a five-year survival rate of a dismal 8.2 percent. 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.”

In the light of this study, the team of researchers have hope that identifying beneficial bacteria that could potentially be utilized to slow the progression of pancreatic cancer or decrease risk is important in future studies

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