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Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer
- Source :
- Nature medicine. 28(2)
- Publication Year :
- 2020
-
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.
- Subjects :
- metagenomics
Lung Neoplasms
Microbiota
Programmed Cell Death 1 Receptor
biomarkers
kidney cancer
General Medicine
Akkermansia
patients stratification
NSCLC
General Biochemistry, Genetics and Molecular Biology
B7-H1 Antigen
Microbiome
immunotherapy
Akkermansia muciniphila
cancer
immune checkpoint inhibitors (ICIs)
tumor microenvironment
Carcinoma, Non-Small-Cell Lung
Tumor Microenvironment
biomarker
Humans
metagenomic
Retrospective Studies
Subjects
Details
- ISSN :
- 1546170X
- Volume :
- 28
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Nature medicine
- Accession number :
- edsair.doi.dedup.....d23c375f531b901126abcd40de031ab5