Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome

作者：Lisa Derosa, Valerio Iebba, Carolina Alves Costa Silva, Gianmarco Piccinno, Guojun Gary Wu, Leonardo Lordello, Bertrand Routy, Naisi Zhao, Cassandra Thélémaque, Roxanne Birebent, Federica Marmorino, Marine Fidelle, Meriem Messaoudene, Andrew Maltez Thomas, Gérard Zalcman, Sylvie Friard, Julien Mazières, Clarisse Audigier-Valette, Denis Moro‐Sibilot, François Goldwasser, Arnaud Scherpereel, Hervé Pegliasco, François Ghiringhelli, Nicole C. Bouchard, Cissé Sow, Ines Darik, Silvia Zoppi, Pierre Ly, Anna Reni, Romain Daillère, Eric C Deutsch, Karla A. Lee, Laura A. Bolte, Johannes R. Björk, Rinse Karel Weersma, Fabrice Barlési, Lucas Padilha, Ana Finzel, Morten L. Isaksen, Bernard J. Escudier, Laurence K. Albiges, David Planchard, Fabrice André, Chiara Cremolini, Stephanie D. Martinez, Benjamin Besse, Liping Zhao, Nicola Segata, Jérôme Wojcik, Guido Kroemer, Laurence Zitvogel · 发表于：Cell · 年份：2024 · DOI：10.1016/j.cell.2024.05.029 · 被引用次数：189 · 研究领域：Gut microbiota and health、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

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.