Trust your gut: harnessing the gut microbiome to fight cancer

Immune checkpoint inhibitors are novel cancer immunotherapeutics that have demonstrated remarkable success in achieving durable remission. Immunotherapeutics exploit the natural function of immune cells to target and eliminate tumour cells. However, more than 80% of patients who are treated with checkpoint inhibitors do not respond. Current research indicates that a range of factors, including tumour microenvironment variability, may impact on the efficacy of immune checkpoint inhibitors. In particular, the gut microbiome has come to the forefront as a possible modulator of treatment success. The composition and function of an individual’s microbiome is tightly intertwined with immune function. Disruption of the gut mucosal barrier or dysregulation of the normal microbiome balance can lead to a pro-inflammatory state conducive to tumour growth, while production of certain microbial metabolites, such as short chain fatty acids and inosine, has been shown to promote an anti-tumourigenic microenvironment and increase checkpoint inhibitor efficacy. This review explores current research on the impacts of the gut microbiome on immune checkpoint efficacy, and strategies for promoting a more conducive microbiome to increase treatment response rates, including faecal microbiota transplant and probiotic supplementation. While clinical trials on potential gut microbiome-modulating adjuvant strategies are still in their infancy, there is promising evidence in support of their efficacy in enhancing immune checkpoint inhibitor therapy.