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A Single-Cell Tumor Immune Atlas for Precision Oncology

Paula Nieto, Marc Elosua-Bayes, Juan L. Trincado, Domenica Marchese, Ramon Massoni-Badosa, Maria Salvany, Ana Henriques, Elisabetta Mereu, Catia Moutinho, Sara Ruiz, Patricia Lorden, Vanessa T. Chin, Dominik Kaczorowski, Chia-Ling Chan, Richard Gallagher, Angela Chou, Ester Planas-Rigol, Carlota Rubio-Perez, View ORCID ProfileIvo Gut, Josep M. Piulats, Joan Seoane, Joseph E. Powell, Eduard Batlle, View ORCID ProfileHolger Heyn
doi: https://doi.org/10.1101/2020.10.26.354829
Paula Nieto
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
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Marc Elosua-Bayes
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
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Juan L. Trincado
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
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Domenica Marchese
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
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Ramon Massoni-Badosa
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
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Maria Salvany
2Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
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Ana Henriques
2Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
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Elisabetta Mereu
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
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Catia Moutinho
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
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Sara Ruiz
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
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Patricia Lorden
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
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Vanessa T. Chin
3Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia
4St Vincent’s Hospital Clinical School, University of New South Wales, Sydney; St Vincent’s Hospital Sydney, Darlinghurst, Australia
5St Vincent’s Hospital Sydney, Darlinghurst, Australia
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Dominik Kaczorowski
3Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia
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Chia-Ling Chan
3Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia
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Richard Gallagher
5St Vincent’s Hospital Sydney, Darlinghurst, Australia
6University of Notre Dame, Sydney, Australia
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Angela Chou
7Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards NSW 065 Australia
8NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney NSW 2065 Australia
9University of Sydney, Sydney, NSW 2006 Australia
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Ester Planas-Rigol
10Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 08035 Barcelona, Spain
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Carlota Rubio-Perez
10Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 08035 Barcelona, Spain
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Ivo Gut
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
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Josep M. Piulats
11Medical Oncology Department, Institut Català d’Oncologia - ICO; Clinical Research in Solid Tumors Group - CREST, Bellvitge Biomedical Research Institute IDIBELL-OncoBell; CIBERONC; L’Hospitalet de Llobregat, Barcelona, Spain
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Joan Seoane
10Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 08035 Barcelona, Spain
12Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
13Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
14CIBERONC, Barcelona, Spain
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Joseph E. Powell
3Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia
15UNSW Cellular Genomics Futures Institute, University of New South Wales, Sydney, Australia
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Eduard Batlle
2Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
12Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
14CIBERONC, Barcelona, Spain
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Holger Heyn
1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
16Universitat Pompeu Fabra (UPF), Barcelona, Spain
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  • ORCID record for Holger Heyn
  • For correspondence: holger.heyn@cnag.crg.eu
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Abstract

The tumor immune microenvironment is a main contributor to cancer progression and a promising therapeutic target for oncology. However, immune microenvironments vary profoundly between patients and biomarkers for prognosis and treatment response lack precision. A comprehensive compendium of tumor immune cells is required to pinpoint predictive cellular states and their spatial localization. We generated a single-cell tumor immune atlas, jointly analyzing >500,000 cells from 217 patients and 13 cancer types, providing the basis for a patient stratification based on immune cell compositions. Projecting immune cells from external tumors onto the atlas facilitated an automated cell annotation system for a harmonized interpretation. To enable in situ mapping of immune populations for digital pathology, we applied SPOTlight, combining single-cell and spatial transcriptomics data and identifying striking spatial immune cell patterns in tumor sections. We expect the tumor immune cell atlas, together with our versatile toolbox for precision oncology, to advance currently applied stratification approaches for prognosis and immuno-therapy.

Competing Interest Statement

JS is co-founder of Mosaic Biomedicals, Board member of Northern-Mosaic partnership and has ownership interests from Mosaic Biomedicals and Northern Biologics. JS received grant/research support from Mosaic Biomedicals, Northern Biologics, Roche/Glycart and Hoffmann la Roche. JS reports scientific consultancy role for Merck Serono, GSK, Eli Lilly. All authors declare no conflicts of interest associated with this manuscript. All other authors declare no conflicts of interest associated with this manuscript.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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A Single-Cell Tumor Immune Atlas for Precision Oncology
Paula Nieto, Marc Elosua-Bayes, Juan L. Trincado, Domenica Marchese, Ramon Massoni-Badosa, Maria Salvany, Ana Henriques, Elisabetta Mereu, Catia Moutinho, Sara Ruiz, Patricia Lorden, Vanessa T. Chin, Dominik Kaczorowski, Chia-Ling Chan, Richard Gallagher, Angela Chou, Ester Planas-Rigol, Carlota Rubio-Perez, Ivo Gut, Josep M. Piulats, Joan Seoane, Joseph E. Powell, Eduard Batlle, Holger Heyn
bioRxiv 2020.10.26.354829; doi: https://doi.org/10.1101/2020.10.26.354829
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A Single-Cell Tumor Immune Atlas for Precision Oncology
Paula Nieto, Marc Elosua-Bayes, Juan L. Trincado, Domenica Marchese, Ramon Massoni-Badosa, Maria Salvany, Ana Henriques, Elisabetta Mereu, Catia Moutinho, Sara Ruiz, Patricia Lorden, Vanessa T. Chin, Dominik Kaczorowski, Chia-Ling Chan, Richard Gallagher, Angela Chou, Ester Planas-Rigol, Carlota Rubio-Perez, Ivo Gut, Josep M. Piulats, Joan Seoane, Joseph E. Powell, Eduard Batlle, Holger Heyn
bioRxiv 2020.10.26.354829; doi: https://doi.org/10.1101/2020.10.26.354829

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