Surrogate markers of intestinal dysfunction associated with survival in advanced cancers

Roxanne Birebent(Inserm), Damien Drubay(Université Paris-Saclay), Carolina Alves Costa Silva(Inserm), Federica Marmorino(University of Pisa), Giacomo Vitali(Inserm), Gianmarco Piccinno(University of Trento), Yoan Hurtado(Inserm), Adele Bonato(Inserm), Lorenzo Belluomini(University of Verona), Meriem Messaoudene(Centre Hospitalier de l’Université de Montréal), Bertrand Routy(Centre Hospitalier de l’Université de Montréal), Marine Fidelle(Inserm), Gérard Zalcman(Université Paris Cité), Julien Mazières(Centre Hospitalier Universitaire de Toulouse), Clarisse Audigier-Valette(Centre Hospitalier Intercommunal Toulon-La Seyne-sur-Mer), Denis Moro‐Sibilot, François Goldwasser(Université Paris Cité), Arnaud Scherpereel(Inserm), Hervé Pegliasco(European Hospital), François Ghiringhelli(Inserm), Anna Reni(University of Verona), Fabrice Barlési(Université Paris-Saclay), Laurence Albigès(Université Paris-Saclay), David Planchard(Université Paris-Saclay), Stéphanie Martinez(Centre Hospitalier Intercommunal Aix-Pertuis), Benjamin Besse(Université Paris-Saclay), Nicola Segata(University of Trento), Chiara Cremolini(University of Pisa), Laurence Zitvogel(Inserm), Valerio Iebba(Institut Gustave Roussy), Lisa Derosa(Inserm)
OncoImmunology
April 6, 2025
Cited by 13Open Access
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Abstract

Akk), while determination of the serum addressin MAdCAM-1 instructs on endothelial gut barrier dysfunction. Here we examined patient survival during chemo-immuno-therapy in 955 cancer patients across four independent cohorts of non-small cell lung (NSCLC), genitourinary (GU) and colorectal (CRC) cancers, according to hallmarks of gut dysbiosis. We show that Akk prevalence represents a stable and favorable phenotype in NSCLC and CRC cancer patients. Over-dominance of Akk above the healthy threshold was observed in dismal prognosis in NSCLC and GU and mirrored an immunosuppressive gut ecosystem and excessive intestinal epithelial exfoliation in NSCLC. In CRC, the combination of a lack of Akk and low sMAdCAM-1 levels identified a subset comprising 28% of patients with reduced survival, independent of the immunoscore. We conclude that gut dysbiosis hallmarks deserve integration within the diagnosis toolbox in oncological practice.


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