Gut flora from a healthy donor could improve the efficacy of immunotherapy used to combat skin cancer, according to work involving Montreal researchers.

The multicentre study, involving the Centre hospitalier de l'Université de Montréal (CHUM) and Montreal's Jewish General Hospital, has shown that transplanting the microbiome of healthy subjects into patients with advanced melanoma is safe, and could enhance the efficacy of immunotherapy treatment.

"We took someone else's stool and gave it to the patient just before he started immunotherapy, and it increased efficacy significantly," summarized CHUM's Dr. Bertrand Routy.

"It's a very good and very big signal for cancer patients," he said.

Immunotherapy treatments encourage the patient's immune system to attack and destroy the cancer. However, they are only effective in around half of all melanoma patients.

In fact, Routy describes a "plateauing, over the last two or three years" in the efficacy of the two immunotherapy treatments currently used to treat melanoma. Life expectancy at five years is 50 per cent for patients with metastatic melanoma.

Researchers are therefore exploring other strategies for taking the next step. In the new study, 20 melanoma patients were recruited from CHUM (which is increasingly positioning itself as one of Canada's leading centres for the study of the oncology microbiome) and the Jewish General Hospital. Participants received the microbiome of a healthy donor one week before the start of their immunotherapy treatment.

The study concluded that the combination of fecal transplantation and immunotherapy is safe, which was the primary objective of this Phase 1 study. The study also found that 65 per cent of patients who preserved the donor microbiome had a clinical response to the combined treatment.

"The results are very encouraging," said Routy.

The exact mechanism by which the microbiome improves the efficacy of immunotherapy is not yet understood, but after five years of work, "we're beginning to understand which bacteria are associated with resistance and which bacteria are associated with the right response," explained Routy.

"When we do a fecal transplant, we're able to eliminate certain bacteria that are associated with resistance to immunotherapy, and we're able to increase those that are associated with a good response," he explained.

Certain mysteries persist, however, such as the "compatibility" between the stool donor and the recipient," continued Routy.

"In a completely different field, for example, it took 30 years to fully understand the compatibility between a bone marrow donor and a recipient," he cited as an example.

At present, fecal transplants in oncology are done somewhat "at random," admitted the researcher, but within three or five years, we should have better knowledge for a more optimal match between donor and recipient.

"You're a patient, you come to the hospital, you're diagnosed with cancer, we look at the composition of the microbiome and we tell you sir, madam, you're missing bacteria ABC, and you've got F and G which are very bad, we're going to give you a transplant from a donor X who will be able to eliminate the bad bacteria and increase the good bacteria you're missing," said Routy.

Researchers will also want to know whether the same fecal transplants would be equally effective among different populations, in North America, Europe and Asia, for example.

The microbiome is a burgeoning field of research, and scientists are discovering more and more unsuspected (and sometimes astounding) associations between our intestinal flora and various facets of our health. According to Routy, this progress is due in part to the fact that, over the last 10 years, we have acquired the tools needed to analyze the composition of the microbiome in detail.

The second phase of the study is already underway, in Quebec and Ontario among other places. In addition to melanoma, researchers will use the opportunity to study the same strategy for other cancers, such as pancreatic and lung cancer, and health problems such as HIV and rheumatoid arthritis.

The findings of this study have been published in the journal Nature Medicine.

This report was first published in French in The Canadian Press on July 10, 2023.