Journal Article

An integrated tumor, immune and microbiome atlas of colon cancer

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

2023

Overview

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. A large, publicly available dataset integrating RNA, whole-exome, T cell receptor and 16S rRNA sequencing from patients with colon cancer enables the discovery of a prognostic score consisting of tumor, immune and microbial features.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/1619/554 / 631/326/2565/2134 / 631/67/1504/1885/1393 / 631/67/580 / Biomarkers / Biomarkers, Tumor - genetics / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cohort Studies / Colon cancer / Colonic Neoplasms - genetics / Colonic Neoplasms - pathology / Colorectal cancer / Cytotoxicity / Datasets / Gene expression / Gene sequencing / Genomic analysis / Humans / Infectious Diseases / Lymphocytes / Lymphocytes T / Metabolic Diseases / Microbiomes / Microorganisms / Microsatellite instability / Molecular Medicine / Neoantigens / Neurosciences / Receptors / Rejection / Resource / Ribonucleic acid / RNA / rRNA 16S / T cell receptors / Transcriptome / Tumor Microenvironment / Tumors / Whole genome sequencing