Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies

Abstract The gut microbiota have long been recognized to play a key role in human health and disease. Currently, several lines of evidence from preclinical to clinical research have gradually established that the gut microbiota can modulate antitumor immunity and affect the efficacy of cancer immunotherapies, especially immune checkpoint inhibitors (ICIs). Deciphering the underlying mechanisms reveals that the gut microbiota reprogram the immunity of the tumor microenvironment (TME) by engaging innate and/or adaptive immune cells. Notably, one of the primary modes by which the gut microbiota modulate antitumor immunity is by means of metabolites, which are small molecules that could spread from their initial location of the gut and impact local and systemic antitumor immune response to promote ICI efficiency. Mechanistic exploration provides novel insights for developing rational microbiota-based therapeutic strategies by manipulating gut microbiota, such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites, to augment the efficacy of ICI and advance the age utilization of microbiota precision medicine.