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Genomic landscape of tumor-host interactions with differential prognostic and predictive connotations

View ORCID ProfileJessica Roelands, View ORCID ProfileWouter Hendrickx, Peter J.K. Kuppen, Raghvendra Mall, Gabriele Zoppoli, Mohamad Saad, Kyle Halliwill, Giuseppe Curigliano, Darawan Rinchai, Julie Decock, Lucia G Delogu, Tolga Turan, Josue Samayoa, Lotfi Chouchane, Ena Wang, Pascal Finetti, Francois Bertucci, Lance D Miller, Jerome Galon, Francesco M Marincola, Michele Ceccarelli, View ORCID ProfileDavide Bedognetti
doi: https://doi.org/10.1101/546069
Jessica Roelands
1Department of Immunology, Inflammation and Metabolism, Division of Translational Medicine, Research Branch, Sidra Medicine, Doha, Qatar
2Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
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  • ORCID record for Jessica Roelands
Wouter Hendrickx
1Department of Immunology, Inflammation and Metabolism, Division of Translational Medicine, Research Branch, Sidra Medicine, Doha, Qatar
3College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Doha, Qatar
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  • For correspondence: dbdognetti@sidra.org whendrickx@sidra.org mceccarelli@abbvie.com
Peter J.K. Kuppen
2Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
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Raghvendra Mall
4Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha, Qatar
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Gabriele Zoppoli
5IRCCS Ospedale Policlinico San Martino, Genova, Italy
6Department of Internal Medicine, University of Genova, Genova, Italy
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Mohamad Saad
4Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha, Qatar
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Kyle Halliwill
7Computational Biology, Computational Oncology and Immunology (CIAO), AbbVie Biotherapeutics, Inc, Redwood City, California, United States of America
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Giuseppe Curigliano
8University of Milano, Department of Oncology and Hemato-Oncology
9European Institute of Oncology, IRCCS, Milano, Italy
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Darawan Rinchai
1Department of Immunology, Inflammation and Metabolism, Division of Translational Medicine, Research Branch, Sidra Medicine, Doha, Qatar
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Julie Decock
10Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar
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Lucia G Delogu
11Istituto di Ricerca Pediatrica, Fondazione Città della Speranza, Padua, Italy
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Tolga Turan
7Computational Biology, Computational Oncology and Immunology (CIAO), AbbVie Biotherapeutics, Inc, Redwood City, California, United States of America
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Josue Samayoa
7Computational Biology, Computational Oncology and Immunology (CIAO), AbbVie Biotherapeutics, Inc, Redwood City, California, United States of America
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Lotfi Chouchane
12Laboratory of Genetic Medicine and Immunology, Weill Cornell Medicine-Qatar, Qatar
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Ena Wang
13Allogene Therapeutics, South San Francisco, California
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Pascal Finetti
14Department of Molecular Oncology, Institut Paoli-Calmettes, Centre de Recherche en Cancerologie de Marseille, UMR1068 Inserm, Marseille, France
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Francois Bertucci
14Department of Molecular Oncology, Institut Paoli-Calmettes, Centre de Recherche en Cancerologie de Marseille, UMR1068 Inserm, Marseille, France
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Lance D Miller
15Wake Forest Comprehensive Cancer Center, Winston-Salem, NC, USA
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Jerome Galon
16INSERM, Laboratory of Integrative Cancer Immunology, Equipe Labellisée Ligue Contre le Cancer, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot; Centre de Recherche des Cordeliers, F-75006 Paris, France
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Francesco M Marincola
17Refuge Biotechnologies, Menlo Park, California, 94025
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Michele Ceccarelli
7Computational Biology, Computational Oncology and Immunology (CIAO), AbbVie Biotherapeutics, Inc, Redwood City, California, United States of America
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  • For correspondence: dbdognetti@sidra.org whendrickx@sidra.org mceccarelli@abbvie.com
Davide Bedognetti
1Department of Immunology, Inflammation and Metabolism, Division of Translational Medicine, Research Branch, Sidra Medicine, Doha, Qatar
3College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Doha, Qatar
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  • ORCID record for Davide Bedognetti
  • For correspondence: dbdognetti@sidra.org whendrickx@sidra.org mceccarelli@abbvie.com
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Abstract

An immune active cancer phenotype typified by a T helper 1 (Th-1) immune response has been associated with increased responsiveness to immunotherapy and favorable prognosis in some but not all cancer types. The reason of this differential prognostic connotation remains unknown. Through a multi-modal Pan-cancer analysis among 31 different histologies (9,282 patients), we demonstrated that the favorable prognostic connotation conferred by the presence of a Th-1 immune response was abolished in tumors displaying specific tumor-cell intrinsic attributes such as high TGF-ß signaling and low proliferation capacity. This observation was validated in the context of immune-checkpoint inhibition. WNT-ß catenin, barrier molecules, Notch, hedgehog, mismatch repair, telomerase activity, and AMPK signaling were the pathways most coherently associated with an immune silent phenotype together with mutations of driver genes including IDH1/2, FOXA2, HDAC3, PSIP1, MAP3K1, KRAS, NRAS, EGFR, FGFR3, WNT5A, and IRF7. Our findings could be used to prioritize hierarchically relevant targets for combination therapies and to refine stratification algorithms.

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  • Revision of main text and reformatted.

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Posted May 08, 2019.
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Genomic landscape of tumor-host interactions with differential prognostic and predictive connotations
Jessica Roelands, Wouter Hendrickx, Peter J.K. Kuppen, Raghvendra Mall, Gabriele Zoppoli, Mohamad Saad, Kyle Halliwill, Giuseppe Curigliano, Darawan Rinchai, Julie Decock, Lucia G Delogu, Tolga Turan, Josue Samayoa, Lotfi Chouchane, Ena Wang, Pascal Finetti, Francois Bertucci, Lance D Miller, Jerome Galon, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
bioRxiv 546069; doi: https://doi.org/10.1101/546069
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Genomic landscape of tumor-host interactions with differential prognostic and predictive connotations
Jessica Roelands, Wouter Hendrickx, Peter J.K. Kuppen, Raghvendra Mall, Gabriele Zoppoli, Mohamad Saad, Kyle Halliwill, Giuseppe Curigliano, Darawan Rinchai, Julie Decock, Lucia G Delogu, Tolga Turan, Josue Samayoa, Lotfi Chouchane, Ena Wang, Pascal Finetti, Francois Bertucci, Lance D Miller, Jerome Galon, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
bioRxiv 546069; doi: https://doi.org/10.1101/546069

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