Microbial partners help fight cancer

One in five cancer patients receives immunotherapy, a treatment that uses the body’s immune system to fight tumors and that is giving great results in lung cancer and melanoma, among others. However, there is an urgent need to continue improving these therapies to benefit more patients.

Now, a team of researchers from Washington University in St. Louis (United States) has discovered in mice that a strain of the intestinal bacteria Ruminococcus gnavus enhances the effects of immunotherapy, EFE reports.

The study, whose results are published in the journal “Science Immunology”, opens up a new strategy once morest cancer: using the gut microbes themselves to reinforce immunotherapy.

“The microbiome plays an important role in mobilizing the body’s immune system to attack cancer cells,” says Marco Colonna, senior author of the study and Professor of Pathology.

“Our findings shed light on a gut bacterial species that helps an immunotherapy drug eliminate tumors in mice. Identifying these microbial partners is an important step in developing probiotics to help improve the efficacy of immunotherapy drugs and benefit more cancer patients,” he said.

Immune cells

Cancer immunotherapy uses the body’s own immune cells to attack and destroy tumors.

One such treatment uses immune checkpoint inhibitor drugs to release the natural brakes that keep immune T cells in check, preventing the body from harming itself. But some tumors fight back by suppressing attacking immune cells, which reduces the effectiveness of these inhibitors.

Colonna’s team conducted a trial in which they completely eliminated sarcoma tumors in mice using a dual inhibition approach.

The researchers first inhibited TREM2, a protein made by tumor macrophages to prevent T cells from attacking the growing tumor, and then showed that a cancer immunotherapy drug was more effective when TREM2 was blocked.

The result indicated that TREM2 dampens the effectiveness of immunotherapy.

Then, in another experiment, the team made a surprising observation: TREM2 mice had the same beneficial response to the checkpoint inhibitor when they were housed with mice lacking the protein.

This occurred when the researchers deviated from their usual protocol of separating the mice before treating them with the inhibitor.

Cohabiting mice share microbes with each other, so the researchers suspected the effects might be due to exchanges of gut bacteria.

By studying the gut microbes of mice successfully treated with immunotherapy, they discovered an expansion of Ruminococcus gnavus, compared to the absence of these microbes in mice that did not respond to the therapy.

R. gnavus has been found in the gut microbiota of cancer patients who respond well to immunotherapy, Colonna says.

In clinical trials, fecal transplants from these people have helped some patients who were unresponsive to immunotherapy reap its benefits.

The researchers introduced R. gnavus into mice and then treated the tumors with a checkpoint inhibitor and found that the tumors shrank, even when TREM2 was used as a weapon to blunt the effect of the immunotherapy.

There is growing evidence that microbiota enhances immunotherapy and identifying relevant species, such as R. gnavus, might lead to a next-generation probiotic that synergizes with immunotherapy to improve oncology care, the authors highlight.

The scientists’ next goal is to understand how R. gnavus contributes to tumor rejection, which might reveal new ways to help cancer patients.