Scientists have discovered a key difference between the few pancreatic cancer patients who survive long-term and the many whose disease overcomes all treatments: the secret lies in the bacterial signatures on their tumors that either stimulate or suppress immune response.
To put it simply, scientists found that the reason why some pancreatic cancer patients can survive for a long time is the bacteria, or microbiome, on the tumor inside their body.
Research also showed that fecal microbiota transplants (FMT) from long-term survivors successfully prompted immune response and stifled tumors in a mouse model of the disease. The transplanted microbiota altered the bacteria on the tumor, or put it in another way, its microbiome.
Why some patients survive
There has been research showing the composition and diversity of microbes living in the digestive tract (the gut microbiome) can affect how cancer immunotherapy works. However, little research has focused on how the bacteria in the tumor might affect prognosis and survival.
That was what drove the researchers: do the bacteria on the tumor have a role in cancer, since we’ve known there are bacteria on pancreatic tumors?
How the study went
The researchers studied on the bacterial DNA in tumors of long-term survivors and short-term survivors, and found that the long-term survivors had much greater diversity of bacterial species than the other group.
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.
They also discovered that long-term survivors showed a relative abundance of 3 kinds of bacteria named Pseudoxanthomonas, Saccharropolyspora and Streptomyces. The presence of all three taxa, as well as the species Bacillus Clausii, predicted better outcomes for patients in the case studies.
How the microbiome helps
Immunohistochemistry showed a greater density of T cells, including the CD8-positive cell-killing variety, in the tumors of long-term survivors. Previous research also showed that more active immune response appeared in long-term survivors.
There is a strong correlation between immune cell infiltration and the microbiome diversity of the tumors, according to McAllister and colleagues. That was also the beginning of finding a solution to change the tumor microbiome.
What FMT is, and how it works
Ready to hear something exciting (and just a little bit disgusting)?
Fecal Microbiota Transplant is a more scientific term for “eating someone else’s poop.”
A fecal transplant is just what it sounds like: someone else’s poop which has been screened for dangerous bacteria, viruses, and is put into another person.
The goal of FMT is to get the good bacteria introduced to a sick person’s tumor to let it help fight against the tumor cells.
How the experiment succeeded on mice
The team compared the bacteria in the gut, in the tumor and in adjacent tissue in three surgery patients. They found the gut microbiome represents about 25% of the tumor microbiome, but is absent from the normal, adjacent tissue, suggesting bacteria in the gut can colonize pancreatic tumors.
The researchers transplanted fecal microbiota from patients with advanced cancer into mice and found that the donor microbiome represented about 5% of the resultant tumor microbiome but that 70% of the overall tumor microbiome had been otherwise altered by the transplant.
"Now we know you can completely change the bacterial composition of the tumor microbiome by doing FMT," Said senior author Florencia McAllister, assistant professor of Clinical Cancer Prevention at MD Anderson.
“Results of the FMT experiments represent a significant therapeutic opportunity to improve pancreatic cancer treatment by altering the tumor immune microenvironment.”
“There is promise here but we have a lot of work ahead.” McAllister added.
A brief introduction to Pancreatic cancer
Pancreatic cancer begins in the tissues of the pancreas, the organ in the abdomen that lies horizontally behind the lower part of the stomach. It can spread rapidly to nearby organs, but it is seldom detected in its early stages, leading it to one of the deadliest cancers.
Common symptoms of pancreatic cancer include jaundice (yellowing of the skin and the whites of the eyes), abdominal pain, back pain, bloating, nausea, vomiting, depression, and fatigue.
Treatment may include surgery, chemotherapy, radiation therapy or a combination of these.