The gut microbiota is considered a key component in many aspects of cancer pathophysiology and response to therapy.,In particular, in recent years intriguing evidences has been emerging regarding the role of the intestinal microbiota in the response to immunotherapy and in promoting the development of adverse events, such as colitis.,For this reason, studies are being carried out both on pre-clinical models and on humans to study how to predict the response to immunotherapy through the study of the microbiota or how to improve its clinical response through modulation.,Promising data have recently been reported through modulation by probiotics or prebiotics, and in particular by fecal microbiota transplantation.,The aim of this review is to analyze the evidence regarding the role of the microbiota in immunotherapy with a particular focus on melanoma.
This is the first prospective study of the effects of human gut microbiota and metabolites on immune checkpoint inhibitor (ICT) response in metastatic melanoma patients.,Whereas many melanoma patients exhibit profound response to ICT, there are fewer options for patients failing ICT-particularly with BRAF-wild-type disease.,In preclinical studies, specific gut microbiota promotes regression of melanoma in mice.,We therefore conducted a study of the effects of pretreatment gut microbiota and metabolites on ICT Response Evaluation Criteria in Solid Tumors response in 39 metastatic melanoma patients treated with ipilimumab, nivolumab, ipilimumab plus nivolumab (IN), or pembrolizumab (P).,IN yielded 67% responses and 8% stable disease; P achieved 23% responses and 23% stable disease.,ICT responders for all types of therapies were enriched for Bacteroides caccae.,Among IN responders, the gut microbiome was enriched for Faecalibacterium prausnitzii, Bacteroides thetaiotamicron, and Holdemania filiformis.,Among P responders, the microbiome was enriched for Dorea formicogenerans.,Unbiased shotgun metabolomics revealed high levels of anacardic acid in ICT responders.,Based on these pilot studies, both additional confirmatory clinical studies and preclinical testing of these bacterial species and metabolites are warranted to confirm their ICT enhancing activity.