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An integrated tumor, immune and microbiome atlas of colon cancer

journal contribution
submitted on 2024-08-27, 07:01 and posted on 2024-08-27, 07:02 authored by Jessica Roelands, Peter J. K. Kuppen, Eiman I. Ahmed, Raghvendra Mall, Tariq Masoodi, Parul Singh, Gianni Monaco, Christophe Raynaud, Noel F.C.C. de Miranda, Luigi Ferraro, Tatiana C. Carneiro-Lobo, Najeeb Syed, Arun Rawat, Amany Awad, Julie Decock, William Mifsud, Lance D. Miller, Shimaa Sherif, Mahmoud G. Mohamed, Darawan Rinchai, Marc Van den Eynde, Rosalyn W. Sayaman, Elad Ziv, Francois Bertucci, Mahir Abdulla Petkar, Stephan Lorenz, Lisa Sara Mathew, Kun Wang, Selvasankar Murugesan, Damien Chaussabel, Alexander L. Vahrmeijer, Ena Wang, Anna Ceccarelli, Khalid A. Fakhro, Gabriele Zoppoli, Alberto Ballestrero, Rob A.E.M. Tollenaar, Francesco M. Marincola, Jérôme Galon, Souhaila Al Khodor, Michele Ceccarelli, Wouter Hendrickx, Davide Bedognetti

The 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.

Other Information

Published in: Nature Medicine
License: https://creativecommons.org/licenses/by/4.0
See article on publisher's website: https://dx.doi.org/10.1038/s41591-023-02324-5

Funding

Qatar National Research Fund (NPRP11S-0121-180351), Towards personalize cancer medicine: Immunoscore and immunogenomic score in primary and metastatic colorectal cancer patients from Europe and Qatar.

Sidra Medicine (SDR100029).

History

Language

  • English

Publisher

Springer Nature

Publication Year

  • 2023

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute - HBKU
  • College of Health and Life Sciences - HBKU
  • Hamad Medical Corporation
  • Women's Wellness and Research Center - HMC
  • Sidra Medicine
  • Clinical Research Centre - Sidra Medicine
  • Weill Cornell Medicine - Qatar

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