Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome.
Fiche publication
Date publication
juin 2024
Journal
Cell
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François
Tous les auteurs :
Derosa L, Iebba V, Silva CAC, Piccinno G, Wu G, Lordello L, Routy B, Zhao N, Thelemaque C, Birebent R, Marmorino F, Fidelle M, Messaoudene M, Thomas AM, Zalcman G, Friard S, Mazieres J, Audigier-Valette C, Sibilot DM, Goldwasser F, Scherpereel A, Pegliasco H, Ghiringhelli F, Bouchard N, Sow C, Darik I, Zoppi S, Ly P, Reni A, Daillère R, Deutsch E, Lee KA, Bolte LA, Björk JR, Weersma RK, Barlesi F, Padilha L, Finzel A, Isaksen ML, Escudier B, Albiges L, Planchard D, André F, Cremolini C, Martinez S, Besse B, Zhao L, Segata N, Wojcik J, Kroemer G, Zitvogel L
Lien Pubmed
Résumé
The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.
Mots clés
Akkermansia muciniphila, PD-(L)1, TOPOSCORE, biomarker, cancer, gut microbiota, immune-checkpoint blockade, immunotherapy, metagenomics, microbiome
Référence
Cell. 2024 06 20;187(13):3373-3389.e16