A New Take on Immunotherapy: Gut Microbes and Tumor Growth

Investigating the microbiome — the collection of microbes that reside in and on our bodies — has provided new insights into infection control, metabolism and mental health. It may also play a significant and surprising role in cancer.

From left, Ashok, Saluja, Ph.D., Vrishketan Sethi, M.B.B.S., and Vikas Dudeja, M.D.

In a study, “Gut Microbiota Promotes Tumor Growth in Mice by Modulating Immune Response,” published April 6 in the journal Gastroenterology, scientists at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine have shown that depleting the gut microbiome reduces tumor growth and metastases in models of pancreatic cancer and melanoma and slows metastases in colon cancer.

“We were surprised to find we could generate this kind of strong immune response simply by depleting gut bacteria,” said Vikas Dudeja, M.D., assistant professor of surgery and co-senior author of the paper. “Modulating the gut microbiome could be a new strategy to fight cancer.”

This work grew out of efforts to understand why so many metastases go to the liver. Knowing the liver hosts many bacteria and bacterial byproducts, the researchers wondered if this might be suppressing the immune response.

To test this out, Vrishketan Sethi, M.B.B.S., a postdoctoral student and the journal article’s first author, gave mouse models of melanoma, pancreatic and colon cancer several antibiotics to deplete their gut microbiomes. The depletion increased the number of T cells producing anti-tumor interferon gamma, while reducing T cells that produce pro-tumor interleukin 10 and 17A.

These immune changes had a dramatic impact on the cancers, shrinking the primary pancreatic and melanoma tumors and reducing liver metastases in all three models.

“Potential cancer treatments are usually so expensive,” noted Ashok Saluja, Ph.D., professor of surgery, and biochemistry and molecular biology, and co-senior author on the paper. “It’s amazing that these antibiotics, which cost next to nothing, can make such a big difference in not only pancreatic cancer but also many other cancers.”

To better understand the mechanism, the team replicated the study in mice that lack mature T and B cells and found depleting the microbiome did not shrink their tumors, indicating the immune system plays a critical role in the process.

Given this success in cancer models, and medicine’s poor track record against pancreatic cancer, this work might quickly make the jump to human studies.

“This approach has the potential to really help patients,” said Saluja. “We are already getting together to plan a very quick clinical trial.”

In addition, at a time when researchers and pharma companies are aggressively hunting for agents that can modulate the immune system and make existing immunotherapy drugs more effective, this approach could be a great fit.

“Though our paper doesn’t address it, this approach could be used to make tumors more sensitive to checkpoint inhibitors,” said Dudeja. “We could also combine regulating the microbiome with other standards of care.”

Tags: Ashok Saluja, microbiome, Vikas Dudeja, Vrishketan Sethi