An integrated tumor, immune and microbiome atlas of colon cancer
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 NaturePublication 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