Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
15
12
2020
accepted:
06
12
2021
pubmed:
5
2
2022
medline:
27
4
2022
entrez:
4
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35115705
doi: 10.1038/s41591-021-01655-5
pii: 10.1038/s41591-021-01655-5
pmc: PMC9330544
mid: NIHMS1807276
doi:
Substances chimiques
B7-H1 Antigen
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
315-324Subventions
Organisme : NCI NIH HHS
ID : R01 CA230551
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA230551
Pays : United States
Organisme : CIHR
Pays : Canada
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
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