Immune checkpoint inhibitors (ICIs) have revolutionized the treatment outcomes for several cancer types that were previously considered incurable. This includes metastatic melanoma, where treatment with ICIs has shown exceptional response and possibly curative effects in a subset of patients. Nonetheless, the majority of patients undergoing ICI therapy do not respond at all. Recently, several studies have identified the patient’s gut microbiota composition as a main factor for mediating response to treatment. We have previously performed a meta-analysis of all published fecal metagenomic whole genome shotgun (WGS) data sets for melanoma patients undergoing ICI therapy (Limeta et al., JCI Insight, 2020). WGS data provides a systematic view of all the species present in the gut and allows us to determine the taxonomic, genomic, and functional differences between responders and non-responders.
We have currently managed to generate 800Gb of additional ultradeep WGS data from an in-house generated data set spanning approx 100 patients. Additionally, we have updated our metagenomic profiling pipeline to the lastest tools for accurate species and gene calling. We are currently planning to re-run all publically available data sets and the in-house data set through the updated pipeline in order to further extract gut microbiome features inherent to response. The outcomes of this study will lead to improved pre-screening of responders in immunotherapy trials and lead to the development of novel probiotic and prebiotic supplements for boosting treatment outcomes in melanoma. Results from this analysis will also help during the design of an upcoming clinical trial together with BioGaia AB in which probiotic supplements will be administered to melanoma patients undergoing checkpoint immunotherapy.