1. Cancer Biology
  2. Immunology and Inflammation
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Topography of cancer-associated immune cells in human solid tumors

  1. Jakob Nikolas Kather  Is a corresponding author
  2. Meggy Suarez-Carmona
  3. Pornpimol Charoentong
  4. Cleo-Aron Weis
  5. Daniela Hirsch
  6. Peter Bankhead
  7. Marcel Horning
  8. Dyke Ferber
  9. Ivan Kel
  10. Esther Herpel
  11. Sarah Schott
  12. Inka Zörnig
  13. Jochen Utikal
  14. Alexander Marx
  15. Timo Gaiser
  16. Herrmann Brenner
  17. Jenny Chang-Claude
  18. Michael Hoffmeister
  19. Dirk Jäger
  20. Niels Halama  Is a corresponding author
  1. National Center for Tumor Diseases (NCT) Heidelberg, Germany
  2. University Medical Center Mannheim, Germany
  3. Queen's University Belfast, United Kingdom
  4. University Hospital Heidelberg, Germany
  5. German Cancer Consortium (DKTK), Germany
  6. German Cancer Research Center (DKFZ), Germany
Research Article
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Cite this article as: eLife 2018;7:e36967 doi: 10.7554/eLife.36967

Abstract

Lymphoid and myeloid cells are abundant in the tumor microenvironment, can be quantified by immunohistochemistry and shape the disease course of human solid tumors. Yet, there is no comprehensive understanding of spatial immune infiltration patterns ('topography') across cancer entities and across various immune cell types. In this study, we systematically measure the topography of multiple immune cell types in 965 histological tissue slides from N=177 patients in a pan-cancer cohort. We provide a definition of inflamed ('hot'), non-inflamed ('cold') and immune excluded patterns and investigate how these patterns differ between immune cell types and between cancer types. In an independent cohort of N=287 colorectal cancer patients, we show that hot, cold and excluded topographies for effector lymphocytes (CD8) and tumor-associated macrophages (CD163) alone are not prognostic, but that a bivariate classification system can stratify patients. Our study adds evidence to consider immune topographies as biomarkers for patients with solid tumors.

Article and author information

Author details

  1. Jakob Nikolas Kather

    Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany
    For correspondence
    jakob.kather@nct-heidelberg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3730-5348
  2. Meggy Suarez-Carmona

    Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Pornpimol Charoentong

    Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Cleo-Aron Weis

    Department of Pathology, University Medical Center Mannheim, Mannheim, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Daniela Hirsch

    Department of Pathology, University Medical Center Mannheim, Mannheim, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Peter Bankhead

    Northern Ireland Molecular Pathology Laboratory, Queen's University Belfast, Belfast, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4851-8813
  7. Marcel Horning

    Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1468-4645
  8. Dyke Ferber

    Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Ivan Kel

    Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1221-7114
  10. Esther Herpel

    Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Sarah Schott

    Department of Gynecology, University Hospital Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Inka Zörnig

    Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  13. Jochen Utikal

    Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Mannheim, Germany
    Competing interests
    The authors declare that no competing interests exist.
  14. Alexander Marx

    Department of Pathology, University Medical Center Mannheim, Mannheim, Germany
    Competing interests
    The authors declare that no competing interests exist.
  15. Timo Gaiser

    Department of Pathology, University Medical Center Mannheim, Mannheim, Germany
    Competing interests
    The authors declare that no competing interests exist.
  16. Herrmann Brenner

    German Cancer Consortium (DKTK), Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  17. Jenny Chang-Claude

    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  18. Michael Hoffmeister

    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  19. Dirk Jäger

    Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  20. Niels Halama

    Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany
    For correspondence
    niels.halama@nct-heidelberg.de
    Competing interests
    The authors declare that no competing interests exist.

Funding

Heidelberg School of Oncology

  • Jakob Nikolas Kather

Bundesministerium für Bildung und Forschung

  • Alexander Marx

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: All experiments were conducted in accordance with the Declaration of Helsinki, the International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS), the Belmont Report and the U.S. Common Rule. Anonymized archival tissue samples were retrieved from the tissue bank of the National Center for Tumor diseases (NCT, Heidelberg, Germany) in accordance with the regulations of the tissue bank and the approval of the ethics committee of Heidelberg University (tissue bank decision numbers 2152 and 2154, granted to NH and JNK, ovarian cancer tissues granted to SS; informed consent was obtained from the patients as part of the NCT tissue bank protocol). Another set of tissue samples was provided by the pathology archive at UMM (University Medical Center Mannheim, Heidelberg University, Mannheim, Germany) after approval by the institutional ethics board (Ethics Board II at University Medical Center Mannheim, decision number 2017-806R-MA, granted to AM and waiving the need for informed consent for this retrospective and fully anonymized analysis of archival samples). Also, a set of melanoma samples was provided by the pathology archive at UMM after approval by the institutional ethics board (Ethics Board II at University Medical Center Mannheim, decision number 2014-835R-MA, granted to JU and waiving the need for informed consent for this retrospective and fully anonymized analysis of archival samples). In addition to this pan-cancer cohort, we acquired a set of N=287 primary surgical specimen of colorectal adenocarcinoma from the DACHS study which were provided by the NCT biobank under the same ethics board approval as stated above and including informed consent by all patients.

Reviewing Editor

  1. Ian Tannock, Princess Margaret Cancer Centre, Canada

Publication history

  1. Received: March 27, 2018
  2. Accepted: August 30, 2018
  3. Accepted Manuscript published: September 4, 2018 (version 1)
  4. Version of Record published: September 11, 2018 (version 2)

Copyright

© 2018, Kather et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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