A team of researchers have provided an association of gut microbiome with immune checkpoint inhibitors (ICIs) response in patients with advanced melanoma. These findings were recently published in the journal Nature Medicine.
ICIs such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are at the forefront of cancer treatment in various cancers, including advanced melanoma. Moreover, the gut microbiome is believed to be associated with clinical responses to ICIs. However, no systematic study has been conducted to determine the characteristics of these responses.
This study involved researchers from various countries who analysed large and diverse cohorts with metagenomic data and determined if the gut microbiome could be used as a biomarker of response to ICI treatment.
Between August 2015 and January 2020, the researchers performed shotgun metagenomic sequencing on stool samples collected from five observations cohorts of patients (n=165) with advanced cutaneous melanoma patients (aged 18 years or older) who were still untreated with ICIs. Additionally, published metagenomic data from 147 samples were integrated into the analysis.
Based on the radiographic response, patients were classified as either responders or non-responders. The overall response rate (ORR) and progression-free survival (PFS) at 12 months were set as clinical endpoints of the study.
An integrated analysis of all the datasets using machine learning found a link between the gut microbiome of patients with advanced melanoma and ORRs, PFS with ICIs. However, no microbiome-based signatures were found across cohorts that could be used as biomarkers for ICI response. The research team did identify a set of species like Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila found in the gut of responders; however, none of these species could be considered as biomarkers.
The meta-analysis of the gut-microbiome of advanced melanoma patients is relatively more complex than assumed. It is pretty challenging to predict the responder or non-responder population based on the differences in the presence/absence of a few microbial species. Future studies with a much larger sample size and integration of other clinical parameters during immunotherapy treatment are suggested.
Lee, K.A., Thomas, A.M., Bolte, L.A. et al. Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma. Nat Med 28, 535–544 (2022). https://doi.org/10.1038/s41591-022-01695-5