How the Gut Microbiome Modulates Immunotherapy of Colon Cancer

Although immune-checkpoint blockade (ICB) dramatically diminishes some solid tumors, it often is ineffective in combating colon cancer. The gut microbiome modulates the effectiveness of ICB (NEJM JW Gen Med Jan 15 2016 and Science 2015; 350:1079), although the mechanisms are unknown.

Using a mouse model for colon cancer, researchers now confirm earlier results indicating that the Bifidobacterium genus (particularly the species B. pseudolongum) enhances the effectiveness of ICB. Moreover, they have identified the mechanism — bacterial production of the metabolite inosine. ICB therapy makes the gut-blood barrier more permeable, which allows inosine (produced by Bifidobacterium species) blood concentrations to rise, leading to systemic activati…