Topography of cancer-associated immune cells in human solid tumors
- National Center for Tumor Diseases (NCT) Heidelberg, Germany
- University Medical Center Mannheim, Germany
- Queen's University Belfast, United Kingdom
- University Hospital Heidelberg, Germany
- German Cancer Consortium (DKTK), Germany
- German Cancer Research Center (DKFZ), Germany
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.
Data availability
We release all source codes under an open access license (doi.org/10.5281/zenodo.1407435; copy archived at https://github.com/elifesciences-publications/immuneTopography). Also, we release all raw data from our experiments (Supplementary File 3).
Article and author information
Author details
Jakob Nikolas Kather
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.
Reviewing Editor
- Ian Tannock, Princess Margaret Cancer Centre, Canada
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.
Version history
- Received: March 27, 2018
- Accepted: August 30, 2018
- Accepted Manuscript published: September 4, 2018 (version 1)
- 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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Topography of cancer-associated immune cells in human solid tumors
eLife 7:e36967.
https://doi.org/10.7554/eLife.36967
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