1. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer
- Author
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Lisa Derosa, Bertrand Routy, Andrew Maltez Thomas, Valerio Iebba, Gerard Zalcman, Sylvie Friard, Julien Mazieres, Clarisse Audigier-Valette, Denis Moro-Sibilot, François Goldwasser, Carolina Alves Costa Silva, Safae Terrisse, Melodie Bonvalet, Arnaud Scherpereel, Hervé Pegliasco, Corentin Richard, François Ghiringhelli, Arielle Elkrief, Antoine Desilets, Felix Blanc-Durand, Fabio Cumbo, Aitor Blanco, Romain Boidot, Sandy Chevrier, Romain Daillère, Guido Kroemer, Laurie Alla, Nicolas Pons, Emmanuelle Le Chatelier, Nathalie Galleron, Hugo Roume, Agathe Dubuisson, Nicole Bouchard, Meriem Messaoudene, Damien Drubay, Eric Deutsch, Fabrice Barlesi, David Planchard, Nicola Segata, Stéphanie Martinez, Laurence Zitvogel, Jean-Charles Soria, Benjamin Besse, Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Deni, Goldwasser, Françoi, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, Françoi, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicola, Le Chatelier, Emmanuelle, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charle, and Besse, Benjamin
- 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 - 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.
- Published
- 2020