Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and gut microbiome

The gut microbiota shapes response to immune checkpoint inhibitors (ICI) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns in 103 Australian and Dutch trial patients treated with neoadjuvant ICI for high-risk resectable metastatic melanoma and performed an integrated analysis with data from 115 US melanoma patients treated with ICI. In these studies, we observed geographically-distinct microbial signatures of response and immune-related adverse events (irAE). Overall however, higher response rates were seen in Ruminococcaceae-dominated microbiomes and lower response rates in Bacteroidaceae-dominated microbiomes. Poor response was associated lower fibre and omega-3 fatty acid consumption, and elevated levels of C-reactive protein in the peripheral circulation at baseline. Together, these data provide novel insight into the relevance of native gut microbiota signatures, dietary intake and systemic inflammation in shaping response and toxicity to ICI, prompting the need for further studies in this area. For metagenomic data, these data sets can be obtained from EGAS00001006982.