An integrated tumor, immune and microbiome atlas of colon cancer
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Published:2023-05
Issue:5
Volume:29
Page:1273-1286
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ISSN:1078-8956
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Container-title:Nature Medicine
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language:en
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Short-container-title:Nat Med
Author:
Roelands JessicaORCID, Kuppen Peter J. K.ORCID, Ahmed Eiman I., Mall RaghvendraORCID, Masoodi TariqORCID, Singh Parul, Monaco Gianni, Raynaud Christophe, de Miranda Noel F.C.C.ORCID, Ferraro Luigi, Carneiro-Lobo Tatiana C., Syed Najeeb, Rawat Arun, Awad Amany, Decock JulieORCID, Mifsud WilliamORCID, Miller Lance D.ORCID, Sherif Shimaa, Mohamed Mahmoud G., Rinchai DarawanORCID, Van den Eynde Marc, Sayaman Rosalyn W.ORCID, Ziv EladORCID, Bertucci Francois, Petkar Mahir AbdullaORCID, Lorenz Stephan, Mathew Lisa SaraORCID, Wang KunORCID, Murugesan Selvasankar, Chaussabel DamienORCID, Vahrmeijer Alexander L.ORCID, Wang Ena, Ceccarelli Anna, Fakhro Khalid A., Zoppoli Gabriele, Ballestrero Alberto, Tollenaar Rob A.E.M., Marincola Francesco M., Galon JérômeORCID, Khodor Souhaila AlORCID, Ceccarelli MicheleORCID, Hendrickx WouterORCID, Bedognetti DavideORCID
Abstract
AbstractThe lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.
Funder
Qatar National Research Fund Associazione Italiana per la Ricerca sul Cancro
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Cited by
18 articles.
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