Gut Microbiome Control of Tumor Immune Checkpoint Inhibitor Response: Mechanistic Insights and Clinical Translation

Here, we summarize available data on mechanisms by which the gut microbiota may affect immune checkpoint inhibitors (ICIs) and discuss potential therapeutic approaches targeting the microbiota. Gut microbiota could affect both antitumor immunity and immune-related toxicities through orchestration of the mucosal and systemic immune response, altering the abundance of functionally relevant taxa, changing community diversity, producing immunomodulatory metabolites, which leads to immunomodulation, inducing innate immunity, modulating adaptive immunity by activation of pattern-recognition pathways, as well as affecting organ crosstalk such as the gut-lung axis, etc. Based on studies of Akkermansia, Bacteroides, short-chain fatty acids, inosine, tryptophan metabolites, or fecal microbiota transplantation, it seems possible that modulating the microbiome could improve response rates to ICI therapy, reduce off-target toxicity, and enable more individualized cancer immunotherapy.