The role of the gut microbiome in regulating the response to immune checkpoint inhibitor therapy

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet the proportion of patients who achieve long-term disease control remain suboptimal. Over the past decade, the gut microbiome has been shown to influence immune-mediated tumour suppression as well as responses to ICI therapies. Compositional differences in gut microbiome may account for the differences in outcomes from immune checkpoint blockade. Identifying microbiota species associated with favourable/unfavourable outcomes and modelling their dynamics throughout the course of ICI treatment could help develop predictive biomarkers of immunotherapy response, and manipulating the gut microbiome represent a novel approach to enhancing ICI effectiveness. Clinically, this raises the prospect of using gut microbiome-based therapies to overcome primary resistance to ICIs, mitigate the effects of microbiome-altering drugs such as antibiotics or proton pump inhibitors, and improve overall survival in patients across numerous different cancer types.