Immunotherapy for cancer patients is impaired by antibiotic use, new study finds

The misuse of antibiotic medicine leading to antibiotic resistance in diseases that they are supposed to help cure has long been understood. New research now shows that taking antibiotics can affect the effectiveness of immunotherapy in cancer patients as well.

A recent study, published in the journal Science this November by a group of experts including those from Gustave Roussy and the French National Institute for Agricultural Research (INRA), showed that prescribed antibiotics can reduce the effectiveness of ongoing immunotherapy. This was found upon exploring the gut microbiota composition of patients through metagenomic analysis.

According to the researchers, more than 20 percent of all cancer patients are currently receiving antibiotic treatment. This is why the findings of the research are so important. The research was conducted with a focus on certain proteins that were then checked for effects in immunotherapy being done on mice.

As part of the study, metagenomic analysis was also used to demonstrate that the bacterium referred to as Akkermansia muciniphila was linked to a better response to anti-PD-1 antibody immunotherapy. That is, having that particular bacterium as part of the microbiome improves the body’s immunotherapy response.

Negative effects of antibiotics

The researchers sampled a group of 249 patients, each being treated with anti-PD-1/PD-L1 based immunotherapy for one of three different cancers: advanced lung cancer, kidney cancer, or bladder cancer. Of these, 28 percent were being given antibiotics for minor infections, and it was clear that their level of health wasn’t that far off from the other patients — those who were not receiving antibiotics.

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What the study revealed was that taking antibiotic medication two months before and up to one month after the first immunotherapy treatment had a negative effect on so-called progression-free survival. The same held true for all patients, regardless of the type of cancer.

To get a closer look at the test results, researchers used metagenomics to establish the precise composition of the gut microbiota both before and during immunotherapy in 153 patients — those with advanced lung or kidney cancer. What they found was that patients who exhibited the best clinical response to immunotherapy had a favorable microbiota composition. In particular, theirs were rich in the bacterium Akkermansia muciniphila.

Improving the worse ones

The next course of action for the researchers was to improve those who showed an unfavorable response to immunotherapy. So they conducted tests on mice to see if receiving the favorable microbiota would change things.

The mice that received the favorable microbiota ended up doing much better when treated with immunotherapy compared with those who received the unfavorable microbiota. And even those in the latter group saw a marked improvement after oral administration of the favorable bacterium. Changing the microbiota lead to a renewed effectiveness of the immunotherapy.

“Our research partially explains why some patients do not respond. Taking antibiotics has a deleterious impact on survival in patients receiving immunotherapy,” explains Dr. Bertrand Routy, hematologist and member of the team of researchers who conducted this study. “Furthermore, the composition of the intestinal microbiota is a new predictive factor for success.”

Immunotherapy is a truly promising new method that has all but changed the way doctors treat various cancers. In most cases where it can be applied, it’s not unusual to see a reduction in tumor size, not to mention a significant increase in overall patient survival. It has also been shown to be superior to standard chemotherapy in advanced cases of cancer, although a majority of patients still don’t benefit from it.

The results of this study will surely push it towards more recognition and eventually, more widespread use.

Sources include:

Gustaveroussy.fr

Nature.com