Gut Bacteria Dramatically Boosts Cancer Immunotherapy

Science has confirmed that a balanced gut—where good bacteria outnumber bad—is often linked to a stronger immune system. Now, researchers in the lab of Thomas Gajewski, professor of pathology and medicine at the University of Chicago (UC), have discovered that good bacteria can also dramatically amplify the effects of cancer immunotherapy treatments. Their results are published in the November issue of the journal Science.

When the researchers introduced a particular strain of bacteria into the digestive tracts of mice with melanoma, they were startled to find it boosted the animals’ immune systems so effectively, the tumor-reducing effects were comparable to anti-cancer drugs known as checkpoint inhibitors, which keep the immune system from becoming overactive.

These inhibitors, however, which can be dramatically effective at reducing tumors when they do work, only do so in a third or fewer patients who use them.

The researchers already knew that gut bacteria had been shown to effect systemic immunity, but they came to their exciting discovery of its effect in cancer treatment by accident. Mice purchased from Jackson Laboratory (JAX) had a more notably robust immune response to small tumors implanted under their skin. Mice from Taconic Biosciences (TAC), however, showed weak immune response. When researchers put the mice from both sources together for three weeks, these discrepancies disappeared. They suspected that the mice shared microbes that enhanced their immunity.

“Gut bacteria influence the differentiation and function of systemic T cell subsets so that they respond faster and more efficiently to stimuli,” says lead author Ayelet Sivan, a Ph.D. student in Gajewski’s lab who designed and executed the experiments.

To test their theory that the microbes were responsible for the improved immune response, they transferred fecal matter from JAX mice to the stomachs of TAC mice, with positive results. The treated TAC mice had stronger immune responses and slower tumor growth.

When they compared the bacterial transfer effects with the effects of a checkpoint inhibitor drug, they found that the bacteria treatment was just as effective.

As soon as five days following the start of fecal transfer, Sivan says, “We saw that there was a delay in tumor outgrowth and that there was a boost in tumor specific immune responses.”

In their search for which specific bacteria made the difference, one genus stood out from over 254 strains: Bifidobacterium. Once identified, they treated the TAC lower-immunity mice with Bifidobacterium directly, without fecal transfer, and still, the immune boosting, tumor-fighting results remained high. 

As for how this occurred, the researchers suspect that Bifidobacterium, which appear to have colonized a compartment in the mouse intestines, interacted with roaming dendritic cells, which hunt for threats and present them to T cells. In response, the T cells attacked the tumors.

Sivan tells mental_floss that their study focused specifically on melanoma cancer because “it is well established that immunotherapies can be effective in melanoma, and that the immune response plays an important role in the control of melanoma growth and treatment.” But future research will look at other cancers that benefit from immunotherapies, as well as other bacteria strains. “There are many open questions as to the mechanism and signals through which Bifidobacterium leads to improved antitumor immunity, which may lead to novel therapies that may eventually replace the use of the bug itself,” she says.

They are eager to get to the stage where the bacteria can be tested for efficacy in humans and will continue to research other bacteria strains and their effect on antitumor immune responses.