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An integrated tumor, immune and microbiome atlas of colon cancer.
- Source :
-
Nature medicine [Nat Med] 2023 May; Vol. 29 (5), pp. 1273-1286. Date of Electronic Publication: 2023 May 19. - Publication Year :
- 2023
-
Abstract
- 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.<br /> (© 2023. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1546-170X
- Volume :
- 29
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Nature medicine
- Publication Type :
- Academic Journal
- Accession number :
- 37202560
- Full Text :
- https://doi.org/10.1038/s41591-023-02324-5