Kill gut bacteria to battle pancreatic cancer, researchers say
Massive bloom in gut microbiome hampers anti-tumour immune reactions. Andrew Masterson reports.
Using antibiotics to remove bacteria populations might significantly improve treatment outcomes for people with a type of pancreatic cancer, research shows.
A study led by scientists from the New York University School of Medicine in the US made the surprising discovery that in humans and mice with pancreatic ductal adenocarcinoma (PDA), a form of cancer that is usually fatal within two years, bacterial colonies in the pancreas increase a staggering 1000-fold.
Not only did the pancreatic microbiome swell, the study found, its composition changed and became dominated by species of bacteria that functioned to prevent the immune system recognising and attacking tumour cells.
The researchers, led by George Miller of New York’s Perlmutter Cancer Centre, found that blitzing the pancreas and gut with antibiotics to dramatically reduce the bacterial population resulted in the immune system recalibrating, recognising the tumour cells and attacking.
Dosing cancer-infected mice with oral antibiotics also increased the efficiency of a type of immunotherapy known as checkpoint inhibition that had previously been found not to work against PDA.
The researchers found that in patients with the cancer, bacteria that normally reside in the gut migrate to the pancreas through a drainage tube called the pancreatic duct. Once there, the colony changes its composition and effectively shuts down immune system responses to tumour cells.
“Our study shows that bacteria change the immune environment around cancer cells to let them grow faster in some patients than others, despite their having the same genetics,” says Miller.
The reasons why the usually benign components of the gut microbiome turn hostile in the pancreas are still being explored. Miller’s team identify two possibilities. In the first, the change is catalysed by the cancer cells themselves, and in the second environmental factors such as diet, other diseases or medications may play a role.
With more research to be done – not least to see if mouse-model results can be replicated in humans – the scientists are not yet ready to claim success in the treatment of PDA. However, the initial signs are promising.
“Our results have implications for understanding immune-suppression in pancreatic cancer and its reversal in the clinic,” says senior co-author Deepak Saxena.
The research is published in the journal Cancer Discovery.