Project 466902

Lung cancer is the most diagnosed cancer and the leading cause of cancer deaths in Canada. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancers, but primary response rates to immune checkpoint inhibitors (ICI), specifically anti-programmed-death-receptor-1 (anti-PD-1) therapy, range from just 15-20%. Studies of the gut microbiome (i.e. the genes associated with microorganisms in the gastrointestinal tract) and tumor mouse models, show that the presence of certain bacteria and high bacterial diversity can improve ICI responses. Emerging data suggest that the Camu-Camu (CC) berry has prebiotic potential to increase levels of beneficial bacteria, decrease tumor size in mice with NSCLC, and transform anti-PD-1 resistant tumors into anti-PD-1 sensitive tumors. Based on these findings, we plan to conduct a clinical trial evaluating the safety and impact of CC on the microbiome and outcomes in patients undergoing anti-PD-1 therapy for advanced NSCLC. Collecting stool samples from patients enrolled in the trial, we will sequence the microbiome and use bioinformatic approaches to identify potential relationships between specific bacteria, immune responses, and treatment outcomes. Alongside the clinical trial, experimental models in NSCLC mice will be used to demonstrate the cause-effect relationship between CC-induced microbiome changes and enhanced ICI response. Transplanting feces from patients into microbiome-free mice, we will reproduce patient microbiomes in mice and test the effects of specific strains of bacteria, with or without CC, on tumor responses. Our project will explore how bacteria interact with prebiotics, strengthen mechanistic findings linking the microbiome to ICI responses in NSCLC, and inform future studies of CC use in other cancers.