Investigating the Synergistic Anti-tumor Effect of Akkermansia and ICI
The gut microbiota plays a salient role in mediating host physiology and immunity. Several studies link immune checkpoint inhibitor (ICI) efficacy in extraintestinal cancers to gut microbiota composition, with commensals, such as Akkermansia muciniphila (A. muciniphila). Recently, studies found that A. muciniphila treatment during anti-PD1 immunotherapy showed potential clinical relevance; however, the differential effects on antitumor responses by the different strains of A. muciniphila are not yet elucidated. Becken et al. (2021) genotyped 71 strains of A. muciniphila, together representing the Am (A. muciniphila) I, AmII, and AmIV clades, and identified clade-specific characteristics that may influence interactions with the host immune system in vivo. Using the collection of A. muciniphila strains from the Valdivia Lab, I will test the hypothesis that A. muciniphila clade-specific traits can lead to varied effects on systemic anti-tumor responses. I will first examine whether gnotobiotic mice colonized with representative A. muciniphila strains from each of the clades exhibit differential anti-tumor responses at baseline and during ICI therapies. I will then examine immune cell populations in the tumor microenvironment.
Message to Sponsor
- Major: MCB
- Sponsor: Anselm MPS Fund
- Mentor: Greg Barton