Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer - Centre de recherche des Cordeliers Access content directly
Journal Articles Nature Medicine Year : 2022

Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Lisa Derosa
Sylvie Friard
  • Function : Author
Melodie Bonvalet
Laurie Alla
  • Function : Author
Nicolas Pons
  • Function : Author
Emmanuelle Le Chatelier
Nathalie Galleron
  • Function : Author
Hugo Roume
  • Function : Author
Agathe Dubuisson
Damien Drubay
Eric Deutsch

Abstract

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics, and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis, and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that may represent potential biomarkers to refine patient stratification in future studies.In a large multicentric study of patients with advanced NSCLC undergoing anti-PD-1 therapy, the relative abundance of intestinal Akkermansia spp. was shown to associate with changes in the gut microbiome ecosystem and clinical outcomes.
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Dates and versions

hal-03978008 , version 1 (02-04-2024)

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Lisa Derosa, Bertrand Routy, Andrew Maltez Thomas, Valerio Iebba, Gerard Zalcman, et al.. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer. Nature Medicine, 2022, 28 (2), pp.315-324. ⟨10.1038/s41591-021-01655-5⟩. ⟨hal-03978008⟩
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