Journal
NATURE MEDICINE
Volume 28, Issue 3, Pages 535-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41591-022-01695-5
Keywords
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Funding
- Seerave Foundation
- European Research Council (ERC-STG project MetaPG)
- MIUR 'Futuro in Ricerca' [RBFR13EWWI_001]
- European H2020 program [ONCOBIOME-825410, MASTER-818368]
- National Cancer Institute of the National Institutes of Health [1U01CA230551]
- Premio Internazionale Lombardia e Ricerca 2019
- Spanish Fondo de Investigaciones Sanitarias of the Instituto de Salud Carlos III, Spain [PI15/00716, PI15/00956]
- European Development Regional Fund A way to achieve Europe
- Wellcome Trust [100282/Z/12/Z]
- Cancer Research UK [A27412, A22902]
- Dutch Cancer Society [10034 POINTING]
- Ministerio de Educacion, Cultura y Deportes, Spain [FPU17/05453]
- Medical Research Council [MR/MO19012/1]
- Harry J. Lloyd Charitable Trust Career Development Award
- Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain [PI15/00716]
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An analysis of metagenomic sequencing of stool samples reveals the association between gut microbiome and response to immune checkpoint blockade therapy in melanoma patients. However, there is limited consistency in the microbiome-based signatures across different populations. Future studies should consider larger sample sizes and examine the complex interplay between clinical factors and the gut microbiome.
An analysis of metagenomic sequencing of stool samples from multiple cohorts of patients with melanoma treated with immune checkpoint blockade uncovers microbiome correlates of response to therapy and also reveals widespread variability across populations. The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific microbiome characteristics linked to the clinical benefits of ICIs. We performed shotgun metagenomic sequencing of stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients with advanced cutaneous melanoma (n = 165). Integrating the dataset with 147 metagenomic samples from previously published studies, we found that the gut microbiome has a relevant, but cohort-dependent, association with the response to ICIs. A machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts. Accordingly, a panel of species, including Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila, associated with responders was identified, but no single species could be regarded as a fully consistent biomarker across studies. Overall, the role of the human gut microbiome in ICI response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and nonresponders. Future studies should adopt larger sample sizes and take into account the complex interplay of clinical factors with the gut microbiome over the treatment course.
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