Consistent Stool Metagenomic Biomarkers Associated with the Response To Melanoma Immunotherapy

Area of Science:

• Microbiology
• Immunology
• Oncology

Background:

• The gut microbiome significantly impacts cancer immunotherapy efficacy, yet reliable biomarkers remain elusive.
• Existing studies show variability in identifying specific gut bacteria associated with treatment response.
• Reanalyzing published data is crucial for a deeper understanding of the gut microbiome's role in immunotherapy.

Purpose of the Study:

• To identify consistent taxonomic and functional metagenomic biomarkers associated with response to melanoma immunotherapy.
• To reanalyze existing metagenomic data to uncover reliable markers for immunotherapy efficacy.
• To validate identified biomarkers using additional datasets, including those related to fecal microbiota transplantation.

Main Methods:

• Analysis of 680 stool metagenomes from 7 independent studies on melanoma patients.
• Comparison of metagenomes between patients with different immunotherapy treatment responses.
• Validation of identified biomarkers on external datasets focusing on fecal microbiota transplantation and immunotherapy response.

Main Results:

• Three bacterial species—Faecalibacterium prausnitzii, Bifidobacterium adolescentis, and Eubacterium rectale—were identified as cross-study taxonomic biomarkers.
• 101 gene groups involved in immune-stimulating molecule/metabolite production were identified as functional biomarkers.
• Faecalibacterium prausnitzii, Eubacterium rectale, and certain Bifidobacterium species were ranked as most beneficial for immunotherapy success.

Conclusions:

• Identified bacterial species and functional gene groups serve as potential biomarkers for melanoma immunotherapy response.
• The findings may explain inconsistencies in previous studies and guide gut microbiome modulation for improved cancer treatment.
• These biomarkers can inform diagnostic test development for predicting patient response to immunotherapy.