Gut-liver connection uncovers new avenues for cancer treatment

Studies have suggested there are links between the gut microbiome, the immune response and cancer, but the role of bacteria in the development of liver cancer is not well understood. A team at the National Cancer Institute has discovered how bacteria in the gut affect anti-tumor immune responses in the liver, a connection that could be exploited to find new therapies for liver cancer. 

The researchers, led by Tim Greten, M.D., of the NCI's Center for Cancer Research, studied three different mouse models of liver cancer. They found that mice given the antibiotic vancomycin to deplete their gut bacteria had smaller and fewer liver tumors than control animals. The antibiotic also seemed to reduce metastasis. 

Further experiments helped them connect the dots. The antibiotic turned out to increase the expression of the protein CXCL16 in endothelial cells, which line the liver's capillaries. That mechanism in turn boosted the quantity of natural killer (NK) T cells in the animals' livers. This accumulation of NKT cells led to the decrease in tumor growth. 

"We asked ourselves, why do mice treated with antibiotics have more CXCL16 production in these endothelial cells?" Greten said in a press release. "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." 

Several companies are testing approaches to exploit the gut microbiome in treating cancer. Last year, Seres Therapeutics announced a collaboration with the MD Anderson Cancer Center to set its microbiome therapy SER-401 with an PD-1 checkpoint inhibitor in melanoma, for example. And Vedanta Biosciences partnered with Japan's JSR to explore the potential of using the microbiome to activate immune-boosting T cells for fighting cancer.

The gut microbiome is being tapped in for treating other diseases, as well. For one, Axial Biotherapeutics is bypassing the blood-brain barrier to treat central nervous system disorders by targeting the gut microbiome instead. 

The NCI researchers discovered that it is the bacterium Clostridium scindens that controls the metabolism of bile acids and ultimately tumor growth in the livers of mice. Although the work is still early, the researchers hope their findings could lay the groundwork for new cancer immunotherapy studies, as they found that bile acids also control CXCL16 expression in humans. The study appears in the journal Science.

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