Researchers from the Center for Cancer Research and the National Cancer Insitute have found that bacteria in the gut plays a role in the liver's anti-tumor immune response. Their work was published today in Science.
"What we found using different tumor models is that if you treat mice with antibiotics and thereby deplete certain bacteria, you can change the composition of immune cells of the liver, affecting tumor growth in the liver," said Tim Greten, who led the study. "This is a great example of how what we learn from basic research can give us insight into cancer and possible treatments."
To study the effect of the gut bacteria, the team carried a number of experiments in three mouse liver cancer models. They found that when the gut bacteria was depleted with an antibiotic cocktail, the mice developed fewer and smaller liver tumors compared to those not given the antibiotic cocktail.
By looking at the immune cells in the liver, they found that when mice were given antibiotics, there were increased numbers of NKT immune cells in the liver, which were the reason why there were reduced tumors. They found that the accumulation of NKT cells in the liver was due to the expression of CXCL16 on cells that line the insides of capillaries in the liver.
"We asked ourselves, why do mice treated with antibiotics have more CXCL16 production in these endothelial cells?" Greten said. "That was the critical point, when we found that bile acids can control the expression of CXCL16. We then did further studies, and found that if we treat mice with bile acids, we can actually change the number of NKT cells in the liver, and thereby the number of tumors in the liver."
Lastly, the team found that the bacteria, Clostridium scindens, controls the metabolism of bile acids in the mouse gut and ultimately CXCL16 expression, NKT cells counts, and liver tumor growth.
The findings from this work not only show a correlation, but a mechanism as well that hopefully can be applied to cancer patients in the future.