Journal
NATURE MEDICINE
Volume 28, Issue 2, Pages 315-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41591-021-01655-5
Keywords
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Funding
- RHU Torino Lumiere [ANR-16-RHUS-0008]
- H2020 ONCOBIOME
- ANR, French-German Ileobiome [19-CE15-0029-01]
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIGN'IT 2020 ARC foundation
- Agence Nationale de la Recherche [ANR-18-IBHU-0002]
- Ligue contre le Cancer (equipe labelisee)
- ANR Projets blancs
- ANR
- ERA-Net for Research on Rare Diseases
- Association Pour La Recherche Sur Le Cancer (ARC)
- Bristol-Myers Squibb (BMS) (International Immuno-Oncology Network)
- Canceropole Ile-de-France
- Chancellerie des Universites de Paris (Legs Poix)
- Fondation pour la Recherche Medicale (FRM)
- Elior
- European Commission (ArtForce)
- European Research Council (ERC)
- Fondation Carrefour
- Institut National du Cancer (INCa)
- Inserm (HTE)
- Institut Universitaire de France
- LeDucq Foundation
- LabEx Immuno-Oncology
- FHU CARE
- Dassault
- Badinter Philantropia
- Paris Alliance of Cancer Research Institutes (PACRI)
- Canadian Institutes of Health Research (CIHR)
- Institut du cancer de Montreal
- Prefontaine family
- CPRIT Research Training Program [RP170067]
- European Research Council (ERC-STG) [MetaPG-716575]
- 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
- BMS
- MSD
- GlaxoSmithKline (GSK)/Tesaro
- Janssen
- Roche/Genentech
- Pfizer
- AstraZeneca
- Amgen
- Agence Nationale de la Recherche (ANR) [ANR-18-IBHU-0002] Funding Source: Agence Nationale de la Recherche (ANR)
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In addition to PD-L1 expression, biomarkers for predicting the response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. This study found that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI treatment in NSCLC patients, independent of PD-L1 expression and other factors. The relative abundance of Akk in the gut microbiome may serve as a potential biomarker for patient stratification.
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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