The gut microbiome has emerged as a hallmark of cancer and a key contributor to influencing clinical outcomes with immune checkpoint inhibitors (ICI) in various cancers. Metagenomics sequencing studies coupled with experiments in germ-free mice have revealed that the gut microbiota bacteria including Akkermansia muciniphila, Ruminococcus and Alistipes were associated with cytotoxic T Helper, CD8+ T cell infiltration, which correlated with improved ICI response. Several clinical studies now focus on modulating the microbiome to enhance the immune response and improve outcomes with ICI, including proof-of-principle fecal microbiota transplantation (FMT) clinical trials in melanoma. Our group recently unravelled the therapeutic potential of castalagin, a prebiotic that beneficially increased anti-PD-1 response in murine models, opening novel therapeutic avenues for patients with cancer.
With the Seerave foundation’s support, we aim over the next two years to further define the mechanism of action of this new prebiotics in order to support the clinical results from our ongoing CC trial.
- Characterize how castalagin induces a shift in bacteria metatranscriptomics
- Assess the direct impact of castalagin on the composition of an entire intestinal microbiota
- Identify the immune-potentiating effects of castalagin on gut immunity and T cell migration toward the tumor microenvironment