Can dietary interventions improve immunotherapy response?

“When immunotherapy emerged a decade ago, we thought it would revolutionize lung cancer treatment,” recalls Dr. Bertrand Routy, a Montreal-based immuno-oncologist whose work focuses on non-small cell lung cancer (NSCLC). “But while some of my patients really benefit from it, many don’t—and we still don’t understand why this happens or how to change it.”

For Dr. Routy, this gap urgently needs addressing so that more patients can benefit from this innovative treatment. That’s why he’ll use funding from a Terry Fox New Investigator Award to search for novel ways to improve immunotherapy response, looking for answers in an unexpected place: the gut microbiome.

The microbiome is the collective name given to the trillions of microbes that live within and on the human body. In recent years, the composition of our gut microbiome – the collection of microbes that live in our digestive tracts – has become a hot topic for cancer researchers like Dr. Routy, who have begun to uncover a relationship between the composition of the gut microbiome and response to immunotherapy.

“In the last couple of years, our team has actually found that the gut microbiota is a key contributor to the patient response to immune checkpoint inhibitors (ICI), the most common type of immunotherapy used in oncology,” explains Dr. Routy. “Indeed, we showed that among the trillions of micro-organisms within the gut microbiota, specific bacterial species were enriched in patients who benefited from ICI.”

Understanding that specific microbes within the gut are contributors to immunotherapy response has pushed Dr. Routy to search for ways to alter the gut microbiome to ensure that those species are present in his patients. That is why as part of his New Investigator project, he will be collaborating with members of the clinical nutrition department at the Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) where he is based, to pioneer a pilot program that seeks to create dietary interventions that he hopes will improve response to immunotherapy.

“We want to determine if nutritional counselling could improve dietary habits that impact the patient microbiota as well as ICI outcome,” explains Dr. Routy, adding that the intervention will focus primarily on increasing dietary fibre, which is a key contributor to a healthy microbiome.

The goal is to get 80 patients with NSCLC to participate in the randomized trial.

In addition to this intervention, Dr. Routy will use funds from a complementary project funded through the Marathon of Hope Cancer Centres Network, to perform multi-omics sequencing of the gut microbiome of these patients before and after the dietary intervention to see exactly how these interventions affect the gut microbiome, and whether they have a downstream impact on immunotherapy response.

“I truly believe that if validated, this would be the biggest discovery in immunotherapy research since the advent of immune-checkpoint inhibitors,” says Dr. Routy.