An integrated tumor, immune and microbiome atlas of colon cancer
TCR metrics and correlation with immune-related genes, immune and molecular subtypes.
A new research by Roelands et al. published in Nature Medicine Journal used a multi-omics approach to thoroughly examine the molecular characteristics of immune responsiveness in colon cancer and uncover interactions between the microbiome and the immune system.
The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. Roelands et al. 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.
The research group identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, they 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.
Dr. Souhaila Al Khodor from Sidra Medicine, researcher in this group, will join Targeting Microbiota 2023 to explain all about the above findings in a talk entitled "Multi-omics in Colon Cancer and Role of the Microbiome".
Image Credits: Roelands et al. Nature Medicine (2023)
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