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

https://www.ncbi.nlm.nih.gov/pubmed/38906102

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.