6:50 PM
May 09, 2019
 |  BC Innovations  |  Targets & Mechanisms

The tumor microbiome emerges as a new source of translational opportunities

The next frontier in microbiome research is bacteria hiding out in tumors

While the gut microbiome has attracted wide attention for its influence on anti-tumor immunity, a growing body of research suggests microbes living in the tumor itself may play even broader roles in cancer. At least two companies are acting on the data, but an early challenge will be sorting out true tumor microbiome signatures from sample contamination.

Since 2015, several high profile studies have linked gut microbiome composition to checkpoint inhibitor response, both as a means of patient stratification and as an opportunity for therapeutic intervention. The connection between gut microbes and anti-tumor immunity lies in the vast numbers of immune cells in lymphoid tissues surrounding the gut, whose activity can be influenced by the bugs (see “Checking Out the Microbiome”).

But it turns out that tumors have their own microbiomes, and early findings suggest they play roles in tumor growth and chemotherapy response, as well as in anti-tumor immunity.

“A tumor is an immune compromised environment, and anaerobic. It makes sense bacteria can survive and thrive there.”

Jonathan Solomon, BiomX

“A tumor is an immune compromised environment, and anaerobic. It makes sense bacteria can survive and thrive there,” said Jonathan Solomon, CEO of BiomX Ltd, which is developing a preclinical phage therapy to treat colorectal cancer.

Research in the nascent field is starting to pick up steam, fueled by improvements in sequencing, cell culture and analysis tools, plus a growing interest in the tumor microenvironment, said Solomon. "There has been work over the last 15-20 years, but in the last year or so, there's been an explosion."

The bulk of the work still falls within the realm of the gut, but focuses on the microbes residing within gastrointestinal cancers. Investigators are also beginning to characterize the microbes that populate tumors in other barrier tissues, such as the skin and lung, and even supposedly sterile tissues like the pancreas.

A key study came from the lab of Ravid Straussman, a professor of molecular and cell biology at the Weizmann Institute of Science, who demonstrated the presence of bacteria in tumor samples from patients with pancreatic ductal adenocarcinoma (PDAC) in a 2017 paper in Science. Straussman is collaborating with Merck KGgA to look for predictive markers of response to PD-1 inhibition in...

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