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

Humans Cohort Studies Biomarkers, Tumor / genetics Colonic Neoplasms / genetics Transcriptome Tumor Microenvironment

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
05 2023
Historique:
received: 29 12 2021
accepted: 28 03 2023
medline: 24 5 2023
pubmed: 19 5 2023
entrez: 18 5 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41591-023-02324-5 PMID: 37202560 PMC: PMC10202816
pubmed: 37202560
doi: 10.1038/s41591-023-02324-5
pii: 10.1038/s41591-023-02324-5
pmc: PMC10202816
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1273-1286

Informations de copyright

© 2023. The Author(s).

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Auteurs

Jessica Roelands (J)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
ORCID: 0000-0003-3631-2041

Peter J K Kuppen (PJK)

Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
ORCID: 0000-0002-0294-3251

Eiman I Ahmed (EI)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.

Raghvendra Mall (R)

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Biotechnology Research Center, Technology Innovation Institute, Abu Dhabi, United Arab Emirates.
ORCID: 0000-0003-1779-3150

Tariq Masoodi (T)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
ORCID: 0000-0002-9186-6349

Parul Singh (P)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.

Gianni Monaco (G)

Institute for Transfusion Medicine and Gene Therapy, Medical Center-University of Freiburg, Freiburg, Germany.
Neuropathology, Medical Center-University of Freiburg, Freiburg, Germany.
BIOGEM Institute of Molecular Biology and Genetics, Ariano Irpino, Italy.

Christophe Raynaud (C)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.

Noel F C C de Miranda (NFCC)

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
ORCID: 0000-0001-6122-1024

Luigi Ferraro (L)

BIOGEM Institute of Molecular Biology and Genetics, Ariano Irpino, Italy.
Department of Electrical Engineering and Information Technology (DIETI), University of Naples Federico II, Naples, Italy.

Tatiana C Carneiro-Lobo (TC)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.

Najeeb Syed (N)

Integrated Genomics Services, Research Branch, Sidra Medicine, Doha, Qatar.

Arun Rawat (A)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.

Amany Awad (A)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.

Julie Decock (J)

Translational Cancer and Immunity Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar.
College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
ORCID: 0000-0002-4409-100X

William Mifsud (W)

Department of Pathology, Sidra Medicine, Doha, Qatar.
Weill-Cornell Medicine Qatar, Doha, Qatar.
ORCID: 0000-0002-9805-6461

Lance D Miller (LD)

Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
ORCID: 0000-0003-3799-2528

Shimaa Sherif (S)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.

Mahmoud G Mohamed (MG)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
Women's Wellness and Research Center, Hamad Medical Corporation, Doha, Qatar.
Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy.

Darawan Rinchai (D)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, USA.
ORCID: 0000-0001-8851-7730

Marc Van den Eynde (M)

Institut Roi Albert II, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.

Rosalyn W Sayaman (RW)

Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
ORCID: 0000-0003-1343-0619

Elad Ziv (E)

Department of Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
ORCID: 0000-0002-2324-2884

Francois Bertucci (F)

Laboratory of Predictive Oncology, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Aix-Marseille Université, Inserm UMR1068, CNRS UMR725, Marseille, France.
Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.

Mahir Abdulla Petkar (MA)

Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar.
ORCID: 0000-0002-0297-8075

Stephan Lorenz (S)

Integrated Genomics Services, Research Branch, Sidra Medicine, Doha, Qatar.

Lisa Sara Mathew (LS)

Integrated Genomics Services, Research Branch, Sidra Medicine, Doha, Qatar.
ORCID: 0000-0003-3177-2233

Kun Wang (K)

Integrated Genomics Services, Research Branch, Sidra Medicine, Doha, Qatar.
ORCID: 0000-0001-9706-5174

Selvasankar Murugesan (S)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.

Damien Chaussabel (D)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
Computational Sciences Department, The Jackson Laboratory, Farmington, CT, USA.
ORCID: 0000-0002-6131-7242

Alexander L Vahrmeijer (AL)

Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
ORCID: 0000-0001-9370-0011

Ena Wang (E)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
Nurix Therapeutics, San Francisco, CA, USA.

Anna Ceccarelli (A)

Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS- Università Cattolica del Sacro Cuore, Rome, Italy.

Khalid A Fakhro (KA)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
Weill-Cornell Medicine Qatar, Doha, Qatar.

Gabriele Zoppoli (G)

Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy.
IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Alberto Ballestrero (A)

Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy.
IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Rob A E M Tollenaar (RAEM)

Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.

Francesco M Marincola (FM)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
Sonata Therapeutics, Watertown, MA, USA.

Jérôme Galon (J)

Inserm, Laboratory of Integrative Cancer Immunology, Equipe Labellisée Ligue Contre Le Cancer, Centre de Recherche de Cordeliers, Université de Paris, Sorbonne Université, Paris, France.
ORCID: 0000-0001-9635-1339

Souhaila Al Khodor (SA)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
ORCID: 0000-0003-4858-7130

Michele Ceccarelli (M)

BIOGEM Institute of Molecular Biology and Genetics, Ariano Irpino, Italy.
Department of Electrical Engineering and Information Technology (DIETI), University of Naples Federico II, Naples, Italy.
Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
ORCID: 0000-0002-4702-6617

Wouter Hendrickx (W)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar. wouterhendrickx79@gmail.com.
College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar. wouterhendrickx79@gmail.com.
ORCID: 0000-0002-7649-5092

Davide Bedognetti (D)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar. davidebedognetti@gmail.com.
College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar. davidebedognetti@gmail.com.
Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy. davidebedognetti@gmail.com.
ORCID: 0000-0002-5857-773X

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › An integrated tumor, immune and microbiome...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › An integrated tumor, immune and microbiome...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › An integrated tumor, immune and microbiome...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Tumeurs de l'intestin › Tumeurs du côlon › An integrated tumor, immune and microbiome...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › An integrated tumor, immune and microbiome...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › An integrated tumor, immune and microbiome...