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Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome
Lisa Derosa (Inserm, Université Paris-Saclay), Valerio Iebba (University of Trieste, Institut Gustave Roussy), Carolina Alves Costa Silva (Inserm, Université Paris-Saclay), Gianmarco Piccinno (University of Trento), Guojun Gary Wu (Rutgers, The State University of New Jersey), Leonardo Lordello (Inserm, Institut Gustave Roussy), Bertrand Routy (Centre Hospitalier de l’Université de Montréal), Naisi Zhao (Tufts University), Cassandra Thélémaque (Inserm, Institut Gustave Roussy), Roxanne Birebent (Inserm, Université Paris-Saclay), Federica Marmorino (University of Pisa, Azienda Ospedaliera Universitaria Pisana), Marine Fidelle (Inserm, Université Paris-Saclay), Meriem Messaoudene (Centre Hospitalier de l’Université de Montréal), Andrew Maltez Thomas (University of Trento), Gérard Zalcman (Université Paris Cité, Assistance Publique – Hôpitaux de Paris), Sylvie Friard (Hôpital Foch), Julien Mazières (Centre Hospitalier Universitaire de Toulouse), Clarisse Audigier-Valette, Denis Moro‐Sibilot (Centre Hospitalier Universitaire de Grenoble), François Goldwasser (Centre National de la Recherche Scientifique, Inserm), Arnaud Scherpereel (Université de Lille, Centre Hospitalier Universitaire de Lille), Hervé Pegliasco (Hôpital Européen), François Ghiringhelli (Inserm, Centre Georges François Leclerc), Nicole Bouchard, Cissé Sow (Inserm, Institut Gustave Roussy), Ines Darik (Inserm, Institut Gustave Roussy), Silvia Zoppi (University of Parma, Inserm), Pierre Ly (Inserm, Institut Gustave Roussy), Anna Reni (University of Verona, Inserm), Romain Daillère (Institut Gustave Roussy), Éric Deutsch (Inserm, Université Paris-Saclay), Karla A. Lee (King's College London), Laura A. Bolte (University Medical Center Groningen, University of Groningen), Johannes R. Björk (University Medical Center Groningen, University of Groningen), Rinse Karel Weersma (University Medical Center Groningen, University of Groningen), Fabrice Barlési (Université Paris-Saclay, Institut Gustave Roussy), Lucas Padilha, Ana Finzel, Morten L. Isaksen, Bernard J. Escudier (Institut Gustave Roussy, Fondation Gustave Roussy), Laurence K. Albiges (Université Paris-Saclay, Institut Gustave Roussy), David Planchard (Université Paris-Saclay, Institut Gustave Roussy), Fabrice André (Université Paris-Saclay, Institut Gustave Roussy), Chiara Cremolini (University of Pisa, Azienda Ospedaliera Universitaria Pisana), Stéphanie Martinez (Centre Hospitalier Intercommunal Aix-Pertuis), Benjamin Besse (Université Paris-Saclay, Institut Gustave Roussy), Liping Zhao (Rutgers, The State University of New Jersey, Shanghai Jiao Tong University), Nicola Segata (University of Trento, European Institute of Oncology), Jérôme Wojcik, Guido Kroemer (Inserm, Institut Universitaire de France), Laurence Zitvogel (Inserm, Université Paris-Saclay)
Abstract: 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.