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Derosa, Lisa; Iebba, Valerio; Silva, Carolina Alves Costa; Piccinno, Gianmarco; Wu, Guojun; Lordello, Leonardo; Routy, Bertrand; Zhao, Naisi; Thelemaque, Cassandra; Birebent, Roxanne; Marmorino, Federica; Fidelle, Marine; Messaoudene, Meriem; Thomas, Andrew Maltez; Zalcman, Gerard; Friard, Sylvie; Mazieres, Julien; Audigier-Valette, Clarisse; Sibilot, Denis Moro; Goldwasser, François; Scherpereel, Arnaud; Pegliasco, Hervé; Ghiringhelli, François; Bouchard, Nicole; Sow, Cissé; Darik, Ines; Zoppi, Silvia; Ly, Pierre; Reni, Anna; Daillère, Romain; Deutsch, Eric; Lee, Karla A.; Bolte, Laura A.; Björk, Johannes R.; Weersma, Rinse K.; Barlesi, Fabrice; Padilha, Lucas; Finzel, Ana; Isaksen, Morten L.; Escudier, Bernard; Albiges, Laurence; Planchard, David; André, Fabrice; Cremolini, Chiara; Martinez, Stéphanie; Besse, Benjamin; Zhao, Liping; Segata, Nicola; Wojcik, Jérôme; Kroemer, Guido; Zitvogel, Laurence
Cell, 06/2024, Letnik: 187, Številka: 13Journal Article
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. Display omitted •Two topological metagenomic bacterial communities are associated with patient survival•A unidimensional dysbiosis score was calculated, allowing survival risk stratification•Gut dysbiosis TOPOSCORE computed from lung cancers could be applied to other cancers•The metagenomics-based score was translated into a rapid 21-bacteria-based qPCR test Topological communities of “favorable or unfavorable” bacteria are functional groups in interaction or competition in the gut. The balance between these anti- or pro-inflammatory communities can be translated into a rapid diagnostic test to evaluate the intestinal dysbiosis associated with survival in patients with lung and kidney cancer.
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