A single-cell tumor immune atlas for precision oncology

  1. Holger Heyn1,16
  1. 1CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain;
  2. 2Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain;
  3. 3Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Sydney, Australia;
  4. 4St. Vincent's Hospital Clinical School, University of New South Wales, Sydney, Australia, and St. Vincent's Hospital Sydney, Darlinghurst NSW 2010, Australia;
  5. 5St. Vincent's Hospital Sydney, Darlinghurst NSW 2010, Australia;
  6. 6University of Notre Dame, Chippendale NSW 2007, Sydney, Australia;
  7. 7Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards NSW 2065, Australia;
  8. 8NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney NSW 2065, Australia;
  9. 9University of Sydney, Sydney NSW 2006, Australia;
  10. 10Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, 08035 Barcelona, Spain;
  11. 11Medical Oncology Department, Institut Català d'Oncologia - ICO; Clinical Research in Solid Tumors Group - CREST, Bellvitge Biomedical Research Institute IDIBELL-OncoBell; CIBERONC; 08908 L'Hospitalet de Llobregat, Barcelona, Spain;
  12. 12Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain;
  13. 13Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain;
  14. 14CIBERONC, 08908 Barcelona, Spain;
  15. 15UNSW Cellular Genomics Futures Institute, University of New South Wales, Sydney NSW 2052, Australia;
  16. 16Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain
  • Corresponding author: holger.heyn{at}cnag.crg.eu

    • 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 published data sets of >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. To enable in situ mapping of immune populations for digital pathology, we applied SPOTlight, combining single-cell and spatial transcriptomics data and identifying colocalization patterns of immune, stromal, and cancer cells 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 immunotherapy.

    Footnotes

    • [Supplemental material is available for this article.]

    • Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.273300.120.

    • Freely available online through the Genome Research Open Access option.

    • Received November 3, 2020.
    • Accepted August 17, 2021.

    This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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    1. Published in Advance September 21, 2021, doi: 10.1101/gr.273300.120 Genome Res. 31: 1913-1926 © 2021 Nieto et al.; Published by Cold Spring Harbor Laboratory Press

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