Grant: Project Grant

The immune system of patients living with cancer is often altered and weakened. Immune checkpoint blockers (ICB) are a new class of drugs that re-awaken the immune system to kill cancer cells that have revolutionized the management of various cancers. Unfortunately, despite unprecedented results, 70% of patients' diseases will progress. Therefore, predictors of response (biomarkers) and ways to safely enhance ICB efficacy are urgently needed. The immune system itself is now known to be influenced by the gut microbiome, which is made up of trillions of bacteria in our intestines that are in constant communication with our immune cells. We pioneered the concept that the gut microbiome influences the clinical response to treatments in both experimental models as well as cancer patients treated with ICB. We demonstrated that antibiotics, by killing pathogens but also beneficial bacteria, negatively impacted clinical outcomes. We also found that lung cancer patients with favorable microbiomes (high bacterial diversity and an abundance of Akkermansia muciniphila bacteria) had a stronger immune response translating into a better clinical outcome. More recently, our unpublished results revealed that in experimental models, a natural prebiotic, Camu Camu, can enhance ICB response. The goal of this project is to demonstrate that Camu Camu can favorably transform the microbiome composition, promoting a stronger ICB anticancer response. To demonstrate our hypothesis, we will sequence feces (gut microbiome) from lung cancer patients treated with ICB. We will then transplant the fecal microbiota of patients into mice who will also receive Camu Camu in order to better understand how prebiotics can improve the microbiome composition and systemic anticancer response. Our ultimate goal is to launch clinical trials based on our results that will use new therapeutic strategies to modify patients' microbiomes, thereby safely increasing ICB effectiveness and improving overall survival.