Manipuler le microbiote intestinal pour augmenter l'efficacité de l'immunothérapie du cancer

 

Bertrand Routy

Centre hospitalier de l'Université de Montréal [CHUM]

 

Domaine : cancer

Programme Chercheurs-boursiers cliniciens - Junior 1

Concours 2019-2020

Immunotherapy represents a major breakthrough in the battle against cancer. Indeed, the immune system of patients living with cancer is often altered and weakened. Immune checkpoint inhibitors (ICI) are a new class of immunotherapy that re-awakens the immune system to directly kill cancer cells. Unfortunately, despite unprecedented results and an increase in survival for patients, 70% will still progress. Therefore, predictors of response (biomarkers) and new ways to safely enhance ICI efficacy are urgently needed.

We unexpectedly found that the gut microbiota (name given to the trillions of bacteria in our gastrointestinal tract) influences the clinical response of patients with advanced lung and renal cancers amenable to ICI. We demonstrated that antibiotics taken prior to starting ICI had a negative effect on patients' survival due to the antibiotic's actions on both harmful bacteria (pathogens) and good bacteria alike. We also found that patients with favorable microbiota (i.e. high bacterial diversity and an abundance of Akkermansia muciniphila bacteria) had a stronger anti-cancer response, translating into a better clinical outcome.

The aim of this project, performed at the CRCHUM (Montreal, Canada) is to validate the role of the microbiota as a new biomarker for patients with lung and renal cell cancer receiving ICI. Furthermore, our objective is to understand how the gut microbiota can influence the bacteria and immune cells present within the tumors. To validate our findings, we plan to transplant patients' feces in mice and study how the microbiota changes with the application of prebiotics (product that help the growth of certain bacteria) with the goal of enhancing the response to immunotherapy.

Our ultimate goal is to develop biomarkers using the gut microbiota, as well as new therapeutic strategies to modify patients' microbiota, in order to safely increase ICI activity.